NKT Cell Activation During (Microbial) Infection

  • Jochen Mattner


Invariant Natural Killer T (iNKT) cells constitute an innate-like lymphocyte population endowed with powerful immunomodulatory functions. Unlike conventional T cells, iNKT cells predominantly express a conserved semi-invariant T cell receptor (TCR), Vα14-Jα18/Vβ2, 7, 8 in mice and Vα24-Jα18/Vβ11 in humans. These canonical TCRs in both species do not recognize peptides, but glycosphingolipid (GSL) patterns presented by CD1d on antigen presenting cells (APCs). The natural mechanisms for iNKT cell activation were unclear prior to the recent identification of their endogenous and exogenous GSL ligands.

Microbes can employ two alternative strategies for iNKT cell activation as exemplarily shown here for Gram-negative bacteria: (a) recognition of endogenous GSLs – by-products of the complex mammalian GSL metabolic pathways – and the presence of interleukin-12 (IL-12), triggered by Toll-like receptor (TLR) signaling of infected APCs, are required for the early secretion of IFN- g by iNKT cells in response to Gram-negative, LPS-positive bacteria. Whereas iNKT cells are secondary to APC-mediated effects in infections with these bacteria, (b) iNKT cells accelerate the clearance of Gram-negative LPS-negative alphaproteobacteria due to the cognate recognition of GSLs in the cell wall of these alphaproteobacteria. Thus, the iNKT cell population represents a major innate recognition pathway for these LPS-negative, GSL-positive alphaproteobacteria that senses infection at sites where iNKT cells accumulate, such as the liver. In this context, iNKT cell activation upon microbial encounter may not only contribute to bacterial clearance, but may be even deleterious for the host, providing innate signals that break peripheral tolerance and unleash autoimmune effector cells.


Major Histocompatibility Complex Major Histocompatibility Complex Class Primary Biliary Cirrhosis iNKT Cell Primary Biliary Cirrhosis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Akbari, O., P. Stock, et al. (2003). “Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity.” Nat Med 9(5): 582–8.PubMedCrossRefGoogle Scholar
  2. Amprey, J. L., J. S. Im, et al. (2004). “A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan.” J Exp Med 200(7): 895–904.PubMedCrossRefGoogle Scholar
  3. Barbeau, J., R. Tanguay, et al. (1996). “Multiparametric analysis of waterline contamination in dental units.” Appl Environ Microbiol 62(11): 3954–9.PubMedGoogle Scholar
  4. Barral, D. C. and M. B. Brenner (2007). “CD1 antigen presentation: how it works.” Nat Rev Immunol 7(12): 929–41.PubMedCrossRefGoogle Scholar
  5. Beckman, E. M. and M. B. Brenner (1995). “MHC class I-like, class II-like and CD1 molecules: distinct roles in immunity.” Immunol Today 16(7): 349–52.PubMedCrossRefGoogle Scholar
  6. Beckman, E. M., S. A. Porcelli, et al. (1994). “Recognition of a lipid antigen by CD1-restricted alpha beta  +  T cells.” Nature 372(6507): 691–4.PubMedCrossRefGoogle Scholar
  7. Beckman, E. M., A. Melian, et al. (1996). “CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family.” J Immunol 157(7): 2795–803.PubMedGoogle Scholar
  8. Behar, S. M., C. C. Dascher, et al. (1999). “Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis.” J Exp Med 189(12): 1973–80.PubMedCrossRefGoogle Scholar
  9. Behar, S. M., T. A. Podrebarac, et al. (1999). “Diverse TCRs recognize murine CD1.” J Immunol 162(1): 161–7.PubMedGoogle Scholar
  10. Bendelac, A. (1995). “CD1: presenting unusual antigens to unusual T lymphocytes.” Science 269(5221): 185–6.PubMedCrossRefGoogle Scholar
  11. Bendelac, A. (1995). “Mouse NK1+ T cells.” Curr Opin Immunol 7(3): 367–74.PubMedCrossRefGoogle Scholar
  12. Bendelac, A. (1995). “Positive selection of mouse NK1+ T cells by CD1-expressing cortical ­thymocytes.” J Exp Med 182(6): 2091–6.PubMedCrossRefGoogle Scholar
  13. Bendelac, A., P. Matzinger, et al. (1992). “Activation events during thymic selection.” J Exp Med 175(3): 731–42.PubMedCrossRefGoogle Scholar
  14. Bendelac, A., N. Killeen, et al. (1994). “A subset of CD4+ thymocytes selected by MHC class I molecules.” Science 263(5154): 1774–8.PubMedCrossRefGoogle Scholar
  15. Bendelac, A., O. Lantz, et al. (1995). “CD1 recognition by mouse NK1+ T lymphocytes.” Science 268(5212): 863–5.PubMedCrossRefGoogle Scholar
  16. Bendelac, A., M. Bonneville, et al. (2001). “Autoreactivity by design: innate B and T lymphocytes.” Nat Rev Immunol 1(3): 177–86.PubMedCrossRefGoogle Scholar
  17. Bendelac, A., P. B. Savage, et al. (2007). “The biology of NKT cells.” Annu Rev Immunol 25: 297–336.PubMedCrossRefGoogle Scholar
  18. Benlagha, K., A. Weiss, et al. (2000). “In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers.” J Exp Med 191(11): 1895–903.PubMedCrossRefGoogle Scholar
  19. Benlagha, K., T. Kyin, et al. (2002). “A thymic precursor to the NK T cell lineage.” Science 296(5567): 553–5.PubMedCrossRefGoogle Scholar
  20. Borg, N. A., K. S. Wun, et al. (2007). “CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor.” Nature 448(7149): 44–9.PubMedCrossRefGoogle Scholar
  21. Brennan, P. J. and H. Nikaido (1995). “The envelope of mycobacteria.” Annu Rev Biochem 64: 29–63.PubMedCrossRefGoogle Scholar
  22. Bricard, G. and S. A. Porcelli (2007). “Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity.” Cell Mol Life Sci 64(14): 1824–40.PubMedCrossRefGoogle Scholar
  23. Brigl, M. and M. B. Brenner (2004). “CD1: antigen presentation and T cell function.” Annu Rev Immunol 22: 817–90.PubMedCrossRefGoogle Scholar
  24. Brigl, M., L. Bry, et al. (2003). “Mechanism of CD1d-restricted natural killer T cell activation during microbial infection.” Nat Immunol 4(12): 1230–7.PubMedCrossRefGoogle Scholar
  25. Brodie, E. L., T. Z. DeSantis, et al. (2007). “Urban aerosols harbor diverse and dynamic bacterial populations.” Proc Natl Acad Sci USA 104(1): 299–304.PubMedCrossRefGoogle Scholar
  26. Brossay, L., D. Jullien, et al. (1997). “Mouse CD1 is mainly expressed on hemopoietic-derived cells.” J Immunol 159(3): 1216–24.PubMedGoogle Scholar
  27. Broxmeyer, H. E., A. Dent, et al. (2007). “A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus.” Exp Hematol 35(4 Suppl 1): 87–93.PubMedCrossRefGoogle Scholar
  28. Brozovic, S., T. Nagaishi, et al. (2004). “CD1d function is regulated by microsomal triglyceride transfer protein.” Nat Med 10(5): 535–9.PubMedCrossRefGoogle Scholar
  29. Burrows, P. D., M. Kronenberg, et al. (2009). “NKT cells turn ten.” Nat Immunol 10(7): 669–71.PubMedCrossRefGoogle Scholar
  30. Busshoff, U., A. Hein, et al. (2001). “CD1 expression is differentially regulated by microglia, macrophages and T cells in the central nervous system upon inflammation and demyelination.” J Neuroimmunol 113(2): 220–30.PubMedCrossRefGoogle Scholar
  31. Calabi, F., K. T. Belt, et al. (1989). “The rabbit CD1 and the evolutionary conservation of the CD1 gene family.” Immunogenetics 30(5): 370–7.PubMedCrossRefGoogle Scholar
  32. Campos-Martin, Y., M. Colmenares, et al. (2006). “Immature human dendritic cells infected with Leishmania infantum are resistant to NK-mediated cytolysis but are efficiently recognized by NKT cells.” J Immunol 176(10): 6172–9.PubMedGoogle Scholar
  33. Cardell, S., S. Tangri, et al. (1995). “CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice.” J Exp Med 182(4): 993–1004.PubMedCrossRefGoogle Scholar
  34. Carnaud, C., D. Lee, et al. (1999). “Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells.” J Immunol 163(9): 4647–50.PubMedGoogle Scholar
  35. Caux, C., C. Dezutter-Dambuyant, et al. (1992). “GM-CSF and TNF-alpha cooperate in the ­generation of dendritic Langerhans cells.” Nature 360(6401): 258–61.PubMedCrossRefGoogle Scholar
  36. Cavicchioli, R., F. Fegatella, et al. (1999). “Sphingomonads from marine environments.” J Ind Microbiol Biotechnol 23(4–5): 268–272.PubMedCrossRefGoogle Scholar
  37. Chan, A. C., L. Serwecinska, et al. (2009). “Immune characterization of an individual with an exceptionally high natural killer T cell frequency and her immediate family.” Clin Exp Immunol 156(2): 238–45.PubMedCrossRefGoogle Scholar
  38. Chang, D. H., K. Osman, et al. (2005). “Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.” J Exp Med 201(9): 1503–17.PubMedCrossRefGoogle Scholar
  39. Chen, Y. H., N. M. Chiu, et al. (1997). “Impaired NK1+ T cell development and early IL-4 production in CD1-deficient mice.” Immunity 6(4): 459–67.PubMedCrossRefGoogle Scholar
  40. Chen, N., C. McCarthy, et al. (2006). “HIV-1 down-regulates the expression of CD1d via Nef.” Eur J Immunol 36(2): 278–86.PubMedCrossRefGoogle Scholar
  41. Chiu, Y. H., J. Jayawardena, et al. (1999). “Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.” J Exp Med 189(1): 103–10.PubMedCrossRefGoogle Scholar
  42. Chiu, Y. H., S. H. Park, et al. (2002). “Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d.” Nat Immunol 3(1): 55–60.PubMedCrossRefGoogle Scholar
  43. Cho, S., K. S. Knox, et al. (2005). “Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complex.” Virology 337(2): 242–52.PubMedCrossRefGoogle Scholar
  44. Cohen, N. R., S. Garg, et al. (2009). “Antigen Presentation by CD1 Lipids, T Cells, and NKT Cells in Microbial Immunity.” Adv Immunol 102: 1–94.PubMedCrossRefGoogle Scholar
  45. Crawford, J. M., J. M. Krisko, et al. (1989). “The distribution of Langerhans cells and CD1a antigen in healthy and diseased human gingiva.” Reg Immunol 2(2): 91–7.PubMedGoogle Scholar
  46. Crowe, N. Y., M. J. Smyth, et al. (2002). “A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas.” J Exp Med 196(1): 119–27.PubMedCrossRefGoogle Scholar
  47. Darmoise, A., S. Teneberg, et al. (2010). “Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells.” Immunity 33(2): 216–28.PubMedCrossRefGoogle Scholar
  48. Dascher, C. C. (2007). “Evolutionary biology of CD1.” Curr Top Microbiol Immunol 314: 3–26.PubMedCrossRefGoogle Scholar
  49. Dascher, C. C. and M. B. Brenner (2003). “Evolutionary constraints on CD1 structure: insights from comparative genomic analysis.” Trends Immunol 24(8): 412–8.PubMedCrossRefGoogle Scholar
  50. Dascher, C. C., K. Hiromatsu, et al. (1999). “Conservation of a CD1 multigene family in the guinea pig.” J Immunol 163(10): 5478–88.PubMedGoogle Scholar
  51. de la Salle, H., S. Mariotti, et al. (2005). “Assistance of microbial glycolipid antigen processing by CD1e.” Science 310(5752): 1321–4.PubMedCrossRefGoogle Scholar
  52. De Libero, G. and L. Mori (2006). “Mechanisms of lipid-antigen generation and presentation to T cells.” Trends Immunol 27(10): 485–92.PubMedCrossRefGoogle Scholar
  53. De Libero, G., A. P. Moran, et al. (2005). “Bacterial infections promote T cell recognition of self-glycolipids.” Immunity 22(6): 763–72.PubMedCrossRefGoogle Scholar
  54. De Santo, C., M. Salio, et al. (2008). “Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans.” J Clin Invest 118(12): 4036–48.Google Scholar
  55. Denkers, E. Y., T. Scharton-Kersten, et al. (1996). “A role for CD4+ NK1.1+ T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8+ effector function against intracellular infection.” J Exp Med 184(1): 131–9.PubMedCrossRefGoogle Scholar
  56. Dieckmann, R., I. Graeber, et al. (2005). “Rapid screening and dereplication of bacterial isolates from marine sponges of the sula ridge by intact-cell-MALDI-TOF mass spectrometry (ICM-MS).” Appl Microbiol Biotechnol 67(4): 539–48.PubMedCrossRefGoogle Scholar
  57. Dougan, S. K., A. Salas, et al. (2005). “Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells.” J Exp Med 202(4): 529–39.PubMedCrossRefGoogle Scholar
  58. Dougan, S. K., P. Rava, et al. (2007). “MTP regulated by an alternate promoter is essential for NKT cell development.” J Exp Med 204(3): 533–45.PubMedCrossRefGoogle Scholar
  59. Duthie, M. S. and S. J. Kahn (2005). “NK cell activation and protection occur independently of natural killer T cells during Trypanosoma cruzi infection.” Int Immunol 17(5): 607–13.PubMedCrossRefGoogle Scholar
  60. Duthie, M. S. and S. J. Kahn (2006). “During acute Trypanosoma cruzi infection highly susceptible mice deficient in natural killer cells are protected by a single alpha-galactosylceramide treatment.” Immunology 119(3): 355–61.PubMedCrossRefGoogle Scholar
  61. Duthie, M. S., M. Kahn, et al. (2005). “Both CD1d antigen presentation and interleukin-12 are required to activate natural killer T cells during Trypanosoma cruzi infection.” Infect Immun 73(3): 1890–4.PubMedCrossRefGoogle Scholar
  62. Duthie, M. S., M. Kahn, et al. (2005). “Critical proinflammatory and anti-inflammatory functions of different subsets of CD1d-restricted natural killer T cells during Trypanosoma cruzi infection.” Infect Immun 73(1): 181–92.PubMedCrossRefGoogle Scholar
  63. Dyall, S. D., M. T. Brown, et al. (2004). “Ancient invasions: from endosymbionts to organelles.” Science 304(5668): 253–7.PubMedCrossRefGoogle Scholar
  64. Eberl, G., R. Lees, et al. (1999). “Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells.” J Immunol 162(11): 6410–9.PubMedGoogle Scholar
  65. Ederer, M. M., R. L. Crawford, et al. (1997). “PCP degradation is mediated by closely related strains of the genus Sphingomonas.” Mol Ecol 6(1): 39–49.PubMedCrossRefGoogle Scholar
  66. Falcone, M., B. Yeung, et al. (1999). “A defect in interleukin 12-induced activation and interferon gamma secretion of peripheral natural killer T cells in nonobese diabetic mice suggests new pathogenic mechanisms for insulin-dependent diabetes mellitus.” J Exp Med 190(7): 963–72.PubMedCrossRefGoogle Scholar
  67. Fischer, K., E. Scotet, et al. (2004). “Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells.” Proc Natl Acad Sci USA 101(29): 10685–90.PubMedCrossRefGoogle Scholar
  68. Fithian, E., P. Kung, et al. (1981). “Reactivity of Langerhans cells with hybridoma antibody.” Proc Natl Acad Sci USA 78(4): 2541–4.PubMedCrossRefGoogle Scholar
  69. Forestier, C., A. Molano, et al. (2005). “Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in (New Zealand Black x New Zealand White)F1 mice.” J Immunol 175(2): 763–70.PubMedGoogle Scholar
  70. Fujii, S., K. Shimizu, et al. (2003). “Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein.” J Exp Med 198(2): 267–79.PubMedCrossRefGoogle Scholar
  71. Fujii, S., K. Liu, et al. (2004). “The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation.” J Exp Med 199(12): 1607–18.PubMedCrossRefGoogle Scholar
  72. Fuss, I. J., F. Heller, et al. (2004). “Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis.” J Clin Invest 113(10): 1490–7.PubMedGoogle Scholar
  73. Galli, G., S. Nuti, et al. (2003). “CD1d-restricted help to B cells by human invariant natural killer T lymphocytes.” J Exp Med 197(8): 1051–7.PubMedCrossRefGoogle Scholar
  74. Galli, G., S. Nuti, et al. (2003). “Innate immune responses support adaptive immunity: NKT cells induce B cell activation.” Vaccine 21 Suppl 2: S48-54.PubMedCrossRefGoogle Scholar
  75. Galli, G., P. Pittoni, et al. (2007). “Invariant NKT cells sustain specific B cell responses and memory.” Proc Natl Acad Sci USA 104(10): 3984–9.PubMedCrossRefGoogle Scholar
  76. Geissmann, F., T. O. Cameron, et al. (2005). “Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids.” PLoS Biol 3(4): e113.PubMedCrossRefGoogle Scholar
  77. Gerlini, G., H. P. Hefti, et al. (2001). “Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells.” J Invest Dermatol 117(3): 576–82.PubMedCrossRefGoogle Scholar
  78. Gershwin, M. E., A. A. Ansari, et al. (2000). “Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.” Immunol Rev 174: 210–25.PubMedCrossRefGoogle Scholar
  79. Giaccone, G., C. J. Punt, et al. (2002). “A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors.” Clin Cancer Res 8(12): 3702–9.PubMedGoogle Scholar
  80. Gilleron, M., S. Stenger, et al. (2004). “Diacylated sulfoglycolipids are novel mycobacterial ­antigens stimulating CD1-restricted T cells during infection with Mycobacterium tuberculosis.” J Exp Med 199(5): 649–59.PubMedCrossRefGoogle Scholar
  81. Glupczynski, Y., W. Hansen, et al. (1984). “Pseudomonas paucimobilis peritonitis in patients treated by peritoneal dialysis.” J Clin Microbiol 20(6): 1225–6.PubMedGoogle Scholar
  82. Godfrey, D. I., S. J. Kinder, et al. (1997). “Flow cytometric study of T cell development in NOD mice reveals a deficiency in alphabetaTCR  +  CDR-CD8- thymocytes.” J Autoimmun 10(3): 279–85.PubMedCrossRefGoogle Scholar
  83. Godfrey, D. I., H. R. MacDonald, et al. (2004). “NKT cells: what’s in a name?” Nat Rev Immunol 4(3): 231–7.PubMedCrossRefGoogle Scholar
  84. Gombert, J. M., A. Herbelin, et al. (1996). “Early quantitative and functional deficiency of NK1  +  −like thymocytes in the NOD mouse.” Eur J Immunol 26(12): 2989–98.PubMedCrossRefGoogle Scholar
  85. Gonzalez-Aseguinolaza, G., L. Van Kaer, et al. (2002). “Natural killer T cell ligand alpha-­galactosylceramide enhances protective immunity induced by malaria vaccines.” J Exp Med 195(5): 617–24.PubMedCrossRefGoogle Scholar
  86. Griewank, K., C. Borowski, et al. (2007). “Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development.” Immunity 27(5): 751–62.PubMedCrossRefGoogle Scholar
  87. Gumperz, J. E., C. Roy, et al. (2000). “Murine CD1d-restricted T cell recognition of cellular ­lipids.” Immunity 12(2): 211–21.PubMedCrossRefGoogle Scholar
  88. Hage, C. A., L. L. Kohli, et al. (2005). “Human immunodeficiency virus gp120 downregulates CD1d cell surface expression.” Immunol Lett 98(1): 131–5.PubMedCrossRefGoogle Scholar
  89. Halden, R. U., B. G. Halden, et al. (1999). “Removal of dibenzofuran, dibenzo-p-dioxin, and 2-chlorodibenzo-p-dioxin from soils inoculated with Sphingomonas sp. strain RW1.” Appl Environ Microbiol 65(5): 2246–9.PubMedGoogle Scholar
  90. Harada, K., K. Isse, et al. (2003). “Accumulating CD57  +  CD3  +  natural killer T cells are related to intrahepatic bile duct lesions in primary biliary cirrhosis.” Liver Int 23(2): 94–100.PubMedCrossRefGoogle Scholar
  91. Hayes, S. M. and K. L. Knight (2001). “Group 1 CD1 genes in rabbit.” J Immunol 166(1): 403–10.PubMedGoogle Scholar
  92. Hong, S., M. T. Wilson, et al. (2001). “The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice.” Nat Med 7(9): 1052–6.PubMedCrossRefGoogle Scholar
  93. Hsueh, P. R., L. J. Teng, et al. (1998). “Nosocomial infections caused by Sphingomonas paucimobilis: clinical features and microbiological characteristics.” Clin Infect Dis 26(3): 676–81.PubMedCrossRefGoogle Scholar
  94. Huang, S., S. Gilfillan, et al. (2008). “MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells.” J Exp Med 205(5): 1201–11.PubMedCrossRefGoogle Scholar
  95. Huber, S., D. Sartini, et al. (2003). “Role of CD1d in coxsackievirus B3-induced myocarditis.” J Immunol 170(6): 3147–53.PubMedGoogle Scholar
  96. Ilyinskii, P. O., R. Wang, et al. (2006). “CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.” J Virol 80(14): 7146–58.PubMedCrossRefGoogle Scholar
  97. Ishikawa, H., H. Hisaeda, et al. (2000). “CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major.” Int Immunol 12(9): 1267–74.PubMedCrossRefGoogle Scholar
  98. Ishikawa, A., S. Motohashi, et al. (2005a). “A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.” Clin Cancer Res 11(5): 1910–7.PubMedCrossRefGoogle Scholar
  99. Ishikawa, E., S. Motohashi, et al. (2005b). “Dendritic cell maturation by CD11c- T cells and Valpha24+ natural killer T-cell activation by alpha-galactosylceramide.” Int J Cancer 117(2): 265–73.PubMedCrossRefGoogle Scholar
  100. Joyce, S. and L. Van Kaer (2003). “CD1-restricted antigen presentation: an oily matter.” Curr Opin Immunol 15(1): 95–104.PubMedCrossRefGoogle Scholar
  101. Joyee, A. G., H. Qiu, et al. (2007). “Distinct NKT cell subsets are induced by different Chlamydia species leading to differential adaptive immunity and host resistance to the infections.” J Immunol 178(2): 1048–58.PubMedGoogle Scholar
  102. Joyee, A. G., H. Qiu, et al. (2008). “Natural killer T cells are critical for dendritic cells to induce immunity in Chlamydial pneumonia.” Am J Respir Crit Care Med 178(7): 745–56.PubMedCrossRefGoogle Scholar
  103. Kakimi, K., L. G. Guidotti, et al. (2000). “Natural killer T cell activation inhibits hepatitis B virus replication in vivo.” J Exp Med 192(7): 921–30.PubMedCrossRefGoogle Scholar
  104. Kang, S. J. and P. Cresswell (2004). “Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells.” Nat Immunol 5(2): 175–81.PubMedCrossRefGoogle Scholar
  105. Kasahara, M. (1997). “New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system.” Hereditas 127(1–2): 59–65.PubMedGoogle Scholar
  106. Kasmar, A., I. Van Rhijn, et al. (2009). “The evolved functions of CD1 during infection.” Curr Opin Immunol 21(4): 397–403.PubMedCrossRefGoogle Scholar
  107. Kawahara, K., H. Kuraishi, et al. (1999). “Chemical structure and function of glycosphingolipids of Sphingomonas spp and their distribution among members of the alpha-4 subclass of Proteobacteria.” J Ind Microbiol Biotechnol 23(4–5): 408–413.PubMedCrossRefGoogle Scholar
  108. Kawahara, K., B. Lindner, et al. (2001). “Structural analysis of a new glycosphingolipid from the lipopolysaccharide-lacking bacterium Sphingomonas adhaesiva.” Carbohydr Res 333(1): 87–93.PubMedCrossRefGoogle Scholar
  109. Kawakami, K., N. Yamamoto, et al. (2003). “Critical role of Valpha14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection.” Eur J Immunol 33(12): 3322–30.PubMedCrossRefGoogle Scholar
  110. Kawano, T., J. Cui, et al. (1997). “CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.” Science 278(5343): 1626–9.PubMedCrossRefGoogle Scholar
  111. Kilic, A., Z. Senses, et al. (2007). “Nosocomial outbreak of Sphingomonas paucimobilis bacteremia in a hemato/oncology unit.” Jpn J Infect Dis 60(6): 394–6.PubMedGoogle Scholar
  112. Kinjo, Y., D. Wu, et al. (2005). “Recognition of bacterial glycosphingolipids by natural killer T cells.” Nature 434(7032): 520–5.PubMedCrossRefGoogle Scholar
  113. Kinjo, Y., E. Tupin, et al. (2006). “Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.” Nat Immunol 7(9): 978–86.PubMedCrossRefGoogle Scholar
  114. Kita, H., O. V. Naidenko, et al. (2002). “Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer.” Gastroenterology 123(4): 1031–43.PubMedCrossRefGoogle Scholar
  115. Kobayashi, E., K. Motoki, et al. (1995). “KRN7000, a novel immunomodulator, and its antitumor activities.” Oncol Res 7(10–11): 529–34.PubMedGoogle Scholar
  116. Koch, M., V. S. Stronge, et al. (2005). “The crystal structure of human CD1d with and without alpha-galactosylceramide.” Nat Immunol 6(8): 819–26.PubMedCrossRefGoogle Scholar
  117. Kronenberg, M. (2005). “Toward an understanding of NKT cell biology: progress and paradoxes.” Annu Rev Immunol 23: 877–900.PubMedCrossRefGoogle Scholar
  118. Kumar, H., A. Belperron, et al. (2000). “Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi.” J Immunol 165(9): 4797–801.PubMedGoogle Scholar
  119. Leadbetter, E. A., M. Brigl, et al. (2008). “NK T cells provide lipid antigen-specific cognate help for B cells.” Proc Natl Acad Sci USA 105(24): 8339–44.PubMedCrossRefGoogle Scholar
  120. Lee, P. T., A. Putnam, et al. (2002). “Testing the NKT cell hypothesis of human IDDM pathogenesis.” J Clin Invest 110(6): 793–800.PubMedGoogle Scholar
  121. Li, Y., P. Thapa, et al. (2009). “Immunologic glycosphingolipidomics and NKT cell development in mouse thymus.” J Proteome Res 8(6): 2740–51.PubMedCrossRefGoogle Scholar
  122. Lin, M. and Y. Rikihisa (2003). “Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival.” Infect Immun 71(9): 5324–31.PubMedCrossRefGoogle Scholar
  123. Lisbonne, M., S. Diem, et al. (2003). “Cutting edge: invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model.” J Immunol 171(4): 1637–41.PubMedGoogle Scholar
  124. Liu, Y., R. D. Goff, et al. (2006). “A modified alpha-galactosyl ceramide for staining and stimulating natural killer T cells.” J Immunol Methods 312(1–2): 34–9.PubMedCrossRefGoogle Scholar
  125. Long, X., S. Deng, et al. (2007). “Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids.” Nat Chem Biol 3(9): 559–64.PubMedCrossRefGoogle Scholar
  126. Mallevaey, T., J. P. Zanetta, et al. (2006). “Activation of invariant NKT cells by the helminth parasite schistosoma mansoni.” J Immunol 176(4): 2476–85.PubMedGoogle Scholar
  127. Mallevaey, T., J. Fontaine, et al. (2007). “Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis.” Infect Immun 75(5): 2171–80.PubMedCrossRefGoogle Scholar
  128. Mars, L. T., J. Novak, et al. (2004). “Therapeutic manipulation of iNKT cells in autoimmunity: modes of action and potential risks.” Trends Immunol 25(9): 471–6.PubMedCrossRefGoogle Scholar
  129. Martino, R., C. Martinez, et al. (1996). “Bacteremia due to glucose non-fermenting gram-negative bacilli in patients with hematological neoplasias and solid tumors.” Eur J Clin Microbiol Infect Dis 15(7): 610–5.PubMedCrossRefGoogle Scholar
  130. Matsuda, J. L., O. V. Naidenko, et al. (2000). “Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers.” J Exp Med 192(5): 741–54.PubMedCrossRefGoogle Scholar
  131. Matsuura, A., M. Kinebuchi, et al. (2000). “NKT cells in the rat: organ-specific distribution of NK T cells expressing distinct V alpha 14 chains.” J Immunol 164(6): 3140–8.PubMedGoogle Scholar
  132. Mattner, J., K. L. Debord, et al. (2005). “Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.” Nature 434(7032): 525–9.PubMedCrossRefGoogle Scholar
  133. Mattner, J., N. Donhauser, et al. (2006). “NKT cells mediate organ-specific resistance against Leishmania major infection.” Microbes Infect 8(2): 354–62.PubMedCrossRefGoogle Scholar
  134. Mattner, J., P. B. Savage, et al. (2008). “Liver autoimmunity triggered by microbial activation of natural killer T cells.” Cell Host Microbe 3(5): 304–15.PubMedCrossRefGoogle Scholar
  135. Meyer, E. H., R. H. DeKruyff, et al. (2007). “iNKT cells in allergic disease.” Curr Top Microbiol Immunol 314: 269–91.PubMedCrossRefGoogle Scholar
  136. Meyer, E. H., R. H. DeKruyff, et al. (2008). “T cells and NKT cells in the pathogenesis of asthma.” Annu Rev Med 59: 281–92.PubMedCrossRefGoogle Scholar
  137. Miller, J., C. Rogers, et al. (2003). “Monitoring the coral disease, plague type II, on coral reefs in St. John, U.S. Virgin Islands.” Rev Biol Trop 51 Suppl 4: 47–55.Google Scholar
  138. Miller, M. M., C. Wang, et al. (2005). “Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family.” Proc Natl Acad Sci USA 102(24): 8674–9.PubMedCrossRefGoogle Scholar
  139. Molano, A., S. H. Park, et al. (2000). “Cutting edge: the IgG response to the circumsporozoite protein is MHC class II-dependent and CD1d-independent: exploring the role of GPIs in NK T cell activation and antimalarial responses.” J Immunol 164(10): 5005–9.PubMedGoogle Scholar
  140. Moody, D. B., B. B. Reinhold, et al. (1997). “Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells.” Science 278(5336): 283–6.PubMedCrossRefGoogle Scholar
  141. Moody, D. B., T. Ulrichs, et al. (2000). “CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection.” Nature 404(6780): 884–8.PubMedCrossRefGoogle Scholar
  142. Moody, D. B., V. Briken, et al. (2002). “Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation.” Nat Immunol 3(5): 435–42.PubMedGoogle Scholar
  143. Moody, D. B., D. C. Young, et al. (2004). “T cell activation by lipopeptide antigens.” Science 303(5657): 527–31.PubMedCrossRefGoogle Scholar
  144. Morita, M., K. Motoki, et al. (1995). “Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.” J Med Chem 38(12): 2176–87.PubMedCrossRefGoogle Scholar
  145. Morrison, A. J., Jr. and J. A. Shulman (1986). “Community-acquired bloodstream infection caused by Pseudomonas paucimobilis: case report and review of the literature.” J Clin Microbiol 24(5): 853–5.PubMedGoogle Scholar
  146. Nestle, F. O., X. G. Zheng, et al. (1993). “Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets.” J Immunol 151(11): 6535–45.PubMedGoogle Scholar
  147. Nichols, K. E., J. Hom, et al. (2005). “Regulation of NKT cell development by SAP, the protein defective in XLP.” Nat Med 11(3): 340–5.PubMedCrossRefGoogle Scholar
  148. Nicol, A., M. Nieda, et al. (2000). “Human invariant valpha24+ natural killer T cells activated by alpha-galactosylceramide (KRN7000) have cytotoxic anti-tumour activity through mechanisms distinct from T cells and natural killer cells.” Immunology 99(2): 229–34.PubMedCrossRefGoogle Scholar
  149. Nieda, M., M. Okai, et al. (2004). “Therapeutic activation of Valpha24  +  Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity.” Blood 103(2): 383–9.PubMedCrossRefGoogle Scholar
  150. Nieuwenhuis, E. E., T. Matsumoto, et al. (2002). “CD1d-dependent macrophage-mediated ­clearance of Pseudomonas aeruginosa from lung.” Nat Med 8(6): 588–93.PubMedCrossRefGoogle Scholar
  151. Ochoa, M. T., A. Loncaric, et al. (2008). “‘Dermal dendritic cells’ comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages.” J Invest Dermatol 128(9): 2225–31.PubMedCrossRefGoogle Scholar
  152. Ohteki, T. and H. R. MacDonald (1994). “Major histocompatibility complex class I related ­molecules control the development of CD4  +  8- and CD4-8- subsets of natural killer 1.1+ T cell receptor-alpha/beta  +  cells in the liver of mice.” J Exp Med 180(2): 699–704.PubMedCrossRefGoogle Scholar
  153. Paget, C., T. Mallevaey, et al. (2007). “Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids.” Immunity 27(4): 597–609.PubMedCrossRefGoogle Scholar
  154. Park, S. H., J. H. Roark, et al. (1998). “Tissue-specific recognition of mouse CD1 molecules.” J Immunol 160(7): 3128–34.PubMedGoogle Scholar
  155. Pasquier, B., L. Yin, et al. (2005). “Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product.” J Exp Med 201(5): 695–701.PubMedCrossRefGoogle Scholar
  156. Peel, M. M., J. M. Davis, et al. (1979). “Pseudomonas paucimobilis from a leg ulcer on a Japanese seaman.” J Clin Microbiol 9(5): 561–4.PubMedGoogle Scholar
  157. Perola, O., T. Nousiainen, et al. (2002). “Recurrent Sphingomonas paucimobilis -bacteraemia associated with a multi-bacterial water-borne epidemic among neutropenic patients.” J Hosp Infect 50(3): 196–201.PubMedCrossRefGoogle Scholar
  158. Pinyakong, O., H. Habe, et al. (2003). “The unique aromatic catabolic genes in sphingomonads degrading polycyclic aromatic hydrocarbons (PAHs).” J Gen Appl Microbiol 49(1): 1–19.PubMedCrossRefGoogle Scholar
  159. Porcelli, S. A. and R. L. Modlin (1999). “The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids.” Annu Rev Immunol 17: 297–329.PubMedCrossRefGoogle Scholar
  160. Porubsky, S., A. O. Speak, et al. (2007). “Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency.” Proc Natl Acad Sci USA 104(14): 5977–82.PubMedCrossRefGoogle Scholar
  161. Procopio, D. O., I. C. Almeida, et al. (2002). “Glycosylphosphatidylinositol-anchored ­mucin-like glycoproteins from Trypanosoma cruzi bind to CD1d but do not elicit dominant innate or adaptive immune responses via the CD1d/NKT cell pathway.” J Immunol 169(7): 3926–33.PubMedGoogle Scholar
  162. Pyz, E., O. Naidenko, et al. (2006). “The complementarity determining region 2 of BV8S2 (V beta 8.2) contributes to antigen recognition by rat invariant NKT cell TCR.” J Immunol 176(12): 7447–55.PubMedGoogle Scholar
  163. Ranson, T., S. Bregenholt, et al. (2005). “Invariant V alpha 14+ NKT cells participate in the early response to enteric Listeria monocytogenes infection.” J Immunol 175(2): 1137–44.PubMedGoogle Scholar
  164. Reina, J., A. Bassa, et al. (1991). “Infections with Pseudomonas paucimobilis: report of four cases and review.” Rev Infect Dis 13(6): 1072–6.PubMedCrossRefGoogle Scholar
  165. Renukaradhya, G. J., T. J. Webb, et al. (2005). “Virus-induced inhibition of CD1d1-mediated ­antigen presentation: reciprocal regulation by p38 and ERK.” J Immunol 175(7): 4301–8.PubMedGoogle Scholar
  166. Rigaud, S., M. C. Fondaneche, et al. (2006). “XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.” Nature 444(7115): 110–4.PubMedCrossRefGoogle Scholar
  167. Roark, J. H., S. H. Park, et al. (1998). “CD1.1 expression by mouse antigen-presenting cells and marginal zone B cells.” J Immunol 160(7): 3121–7.PubMedGoogle Scholar
  168. Roberts, T. J., V. Sriram, et al. (2002). “Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells.” J Immunol 168(11): 5409–14.PubMedGoogle Scholar
  169. Roberts, T. J., Y. Lin, et al. (2004). “CD1d1-dependent control of the magnitude of an acute ­antiviral immune response.” J Immunol 172(6): 3454–61.PubMedGoogle Scholar
  170. Romero, J. F., G. Eberl, et al. (2001). “CD1d-restricted NK T cells are dispensable for specific antibody responses and protective immunity against liver stage malaria infection in mice.” Parasite Immunol 23(5): 267–9.PubMedCrossRefGoogle Scholar
  171. Rosat, J. P., E. P. Grant, et al. (1999). “CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ alpha beta T cell pool.” J Immunol 162(1): 366–71.PubMedGoogle Scholar
  172. Rosenberg, E. and Y. Ben-Haim (2002). “Microbial diseases of corals and global warming.” Environ Microbiol 4(6): 318–26.PubMedCrossRefGoogle Scholar
  173. Salazar, R., R. Martino, et al. (1995). “Catheter-related bacteremia due to Pseudomonas paucimobilis in neutropenic cancer patients: report of two cases.” Clin Infect Dis 20(6): 1573–4.PubMedCrossRefGoogle Scholar
  174. Salomonsen, J., M. R. Sorensen, et al. (2005). “Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC.” Proc Natl Acad Sci USA 102(24): 8668–73.PubMedCrossRefGoogle Scholar
  175. Saltissi, D. and D. J. Macfarlane (1994). “Successful treatment of Pseudomonas paucimobilis haemodialysis catheter-related sepsis without catheter removal.” Postgrad Med J 70(819): 47–8.PubMedCrossRefGoogle Scholar
  176. Schofield, L., M. J. McConville, et al. (1999). “CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells.” Science 283(5399): 225–9.PubMedCrossRefGoogle Scholar
  177. Selmi, C., D. L. Balkwill, et al. (2003). “Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium.” Hepatology 38(5): 1250–7.PubMedCrossRefGoogle Scholar
  178. Selmi, C., M. J. Mayo, et al. (2004). “Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment.” Gastroenterology 127(2): 485–92.PubMedCrossRefGoogle Scholar
  179. Sharif, S., G. A. Arreaza, et al. (2001). “Activation of natural killer T cells by alpha-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes.” Nat Med 7(9): 1057–62.PubMedCrossRefGoogle Scholar
  180. Shi, T., J. K. Fredrickson, et al. (2001). “Biodegradation of polycyclic aromatic hydrocarbons by Sphingomonas strains isolated from the terrestrial subsurface.” J Ind Microbiol Biotechnol 26(5): 283–9.PubMedCrossRefGoogle Scholar
  181. Shimamura, M. (2008). “Glycolipid stimulators for NKT cells bearing invariant V alpha 19-J alpha 33 TCR alpha chains.” Mini Rev Med Chem 8(3): 285–9.PubMedCrossRefGoogle Scholar
  182. Shimamura, M., N. Okamoto, et al. (2006). “Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Valpha19 NKT cell with alpha-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit.” Eur J Med Chem 41(5): 569–76.PubMedCrossRefGoogle Scholar
  183. Shimamura, M., Y. Y. Huang, et al. (2007). “Modulation of Valpha19 NKT cell immune responses by alpha-mannosyl ceramide derivatives consisting of a series of modified sphingosines.” Eur J Immunol 37(7): 1836–44.PubMedCrossRefGoogle Scholar
  184. Sholl, L. M., J. L. Hornick, et al. (2007). “Immunohistochemical analysis of langerin in langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases.” Am J Surg Pathol 31(6): 947–52.PubMedCrossRefGoogle Scholar
  185. Skold, M., X. Xiong, et al. (2005). “Interplay of cytokines and microbial signals in regulation of CD1d expression and NKT cell activation.” J Immunol 175(6): 3584–93.PubMedGoogle Scholar
  186. Song, L., S. Asgharzadeh, et al. (2009). “Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages.” J Clin Invest 119(6): 1524–36.PubMedCrossRefGoogle Scholar
  187. Southern, P. M., Jr. and A. E. Kutscher (1981). “Pseudomonas paucimobilis bacteremia.” J Clin Microbiol 13(6): 1070–3.PubMedGoogle Scholar
  188. Spada, F. M., Y. Koezuka, et al. (1998). “CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells.” J Exp Med 188(8): 1529–34.PubMedCrossRefGoogle Scholar
  189. Speak, A. O., M. Salio, et al. (2007). “Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals.” Proc Natl Acad Sci USA 104(14): 5971–6.PubMedCrossRefGoogle Scholar
  190. Sriram, V., W. Du, et al. (2005). “Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells.” Eur J Immunol 35(6): 1692–701.PubMedCrossRefGoogle Scholar
  191. Stanic, A. K., A. D. De Silva, et al. (2003). “Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by beta-D-glucosylceramide synthase deficiency.” Proc Natl Acad Sci USA 100(4): 1849–54.PubMedCrossRefGoogle Scholar
  192. Stanley, A. C., Y. Zhou, et al. (2008). “Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis.” PLoS Pathog 4(2): e1000028.PubMedCrossRefGoogle Scholar
  193. Stetson, D. B., M. Mohrs, et al. (2003). “Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function.” J Exp Med 198(7): 1069–76.PubMedCrossRefGoogle Scholar
  194. Stevenson, H. L., E. C. Crossley, et al. (2008). “Regulatory roles of CD1d-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis.” Infect Immun 76(4): 1434–44.PubMedCrossRefGoogle Scholar
  195. Swann, J., N. Y. Crowe, et al. (2004). “Regulation of antitumour immunity by CD1d-restricted NKT cells.” Immunol Cell Biol 82(3): 323–31.PubMedCrossRefGoogle Scholar
  196. Szalay, G., C. H. Ladel, et al. (1999). “Cutting edge: anti-CD1 monoclonal antibody treatment reverses the production patterns of TGF-beta 2 and Th1 cytokines and ameliorates listeriosis in mice.” J Immunol 162(12): 6955–8.PubMedGoogle Scholar
  197. Terabe, M. and J. A. Berzofsky (2008). “The role of NKT cells in tumor immunity.” Adv Cancer Res 101: 277–348.PubMedCrossRefGoogle Scholar
  198. Terabe, M., S. Matsui, et al. (2000). “NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway.” Nat Immunol 1(6): 515–20.PubMedCrossRefGoogle Scholar
  199. Tonti, E., G. Galli, et al. (2009). “NKT-cell help to B lymphocytes can occur independently of cognate interaction.” Blood 113(2): 370–6.PubMedCrossRefGoogle Scholar
  200. Tsuneyama, K., M. Yasoshima, et al. (1998). “Increased CD1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis.” Hepatology 28(3): 620–3.PubMedCrossRefGoogle Scholar
  201. Uldrich, A. P., N. Y. Crowe, et al. (2005). “NKT cell stimulation with glycolipid antigen in vivo: costimulation-dependent expansion, Bim-dependent contraction, and hyporesponsiveness to further antigenic challenge.” J Immunol 175(5): 3092–101.PubMedGoogle Scholar
  202. van Dieren, J. M., C. J. van der Woude, et al. (2007). “Roles of CD1d-restricted NKT cells in the intestine.” Inflamm Bowel Dis 13(9): 1146–52.PubMedCrossRefGoogle Scholar
  203. Van Kaer, L. (2005). “alpha-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles.” Nat Rev Immunol 5(1): 31–42.PubMedCrossRefGoogle Scholar
  204. Van Rhijn, I., A. P. Koets, et al. (2006). “The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d.” J Immunol 176(8): 4888–93.PubMedGoogle Scholar
  205. Vilarinho, S., K. Ogasawara, et al. (2007). “Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus.” Proc Natl Acad Sci USA 104(46): 18187–92.PubMedCrossRefGoogle Scholar
  206. von Loewenich, F. D., D. G. Scorpio, et al. (2004). “Frontline: control of Anaplasma phagocytophilum, an obligate intracellular pathogen, in the absence of inducible nitric oxide synthase, phagocyte NADPH oxidase, tumor necrosis factor, Toll-like receptor (TLR)2 and TLR4, or the TLR adaptor molecule MyD88.” Eur J Immunol 34(7): 1789–97.CrossRefGoogle Scholar
  207. Wiethe, C., A. Debus, et al. (2008). “Dendritic cell differentiation state and their interaction with NKT cells determine Th1/Th2 differentiation in the murine model of Leishmania major infection.” J Immunol 180(7): 4371–81.PubMedGoogle Scholar
  208. Winau, F., V. Schwierzeck, et al. (2004). “Saposin C is required for lipid presentation by human CD1b.” Nat Immunol 5(2): 169–74.PubMedCrossRefGoogle Scholar
  209. Woltman, A. M., M. J. Ter Borg, et al. (2009). “Alpha-galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial.” Antivir Ther 14(6): 809–18.PubMedCrossRefGoogle Scholar
  210. Xia, C., Q. Yao, et al. (2006). “Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3).” Bioorg Med Chem Lett 16(8): 2195–9.PubMedCrossRefGoogle Scholar
  211. Yabuuchi, E., I. Yano, et al. (1990). “Proposals of Sphingomonas paucimobilis gen. nov. and comb. nov., Sphingomonas parapaucimobilis sp. nov., Sphingomonas yanoikuyae sp. nov., Sphingomonas adhaesiva sp. nov., Sphingomonas capsulata comb. nov., and two genospecies of the genus Sphingomonas.” Microbiol Immunol 34(2): 99–119.PubMedGoogle Scholar
  212. Yin, L., U. Al-Alem, et al. (2003). “Mice deficient in the X-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia.” J Med Virol 71(3): 446–55.PubMedCrossRefGoogle Scholar
  213. Yuan, W., A. Dasgupta, et al. (2006). “Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling.” Nat Immunol 7(8): 835–42.PubMedCrossRefGoogle Scholar
  214. Zajonc, D. M., C. Cantu, 3 rd, et al. (2005). “Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.” Nat Immunol 6(8): 810–8.PubMedCrossRefGoogle Scholar
  215. Zeng, D., M. Dick, et al. (1998). “Subsets of transgenic T cells that recognize CD1 induce or prevent murine lupus: role of cytokines.” J Exp Med 187(4): 525–36.PubMedCrossRefGoogle Scholar
  216. Zeng, D., M. K. Lee, et al. (2000). “Cutting edge: a role for CD1 in the pathogenesis of lupus in NZB/NZW mice.” J Immunol 164(10): 5000–4.PubMedGoogle Scholar
  217. Zeng, D., Y. Liu, et al. (2003). “Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus.” J Clin Invest 112(8): 1211–22.PubMedGoogle Scholar
  218. Zhou, D., C. Cantu, 3 rd, et al. (2004). “Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins.” Science 303(5657): 523–7.PubMedCrossRefGoogle Scholar
  219. Zhou, D., J. Mattner, et al. (2004). “Lysosomal glycosphingolipid recognition by NKT cells.” Science 306(5702): 1786–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2012

Authors and Affiliations

  1. 1.Microbiology Institute–Clinical Microbiology, Immunology and HygieneUniversity Hospital of ErlangenErlangenGermany

Personalised recommendations