• Yuki Kinjo
  • Mitchell Kronenberg
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 633)

1 Introduction

Natural killer T (NKT) cells combine features of the innate and adaptive immune systems. For example, they are lymphocytes that express an αβ T cell antigen receptor (TCR), typical of adaptive immunity, but they also express NK receptors, such as NK1.1 (NKR-P1 or CD161c), similar to NK cells, which are part of the innate immune system.1, 2 In mice, the majority of NKT cells express an invariant (i) TCRα chain with Vα14–Jα18 rearrangement.1, 2 We refer to these lymphocytes here as Vα14iNKT cells. These cells have a limited repertoire of TCRβ chains, mainly Vβ8.2, Vβ7, and Vβ2, with the highest representation of Vβ8.2 (more than 50%). Humans have a similar population that mostly expresses an invariant Vα24–Jα18 rearrangement with Vβ11 (Vα24iNKT).1, 2 We refer to these two populations in mice and humans as iNKT cells.

iNKT cells have several unique features. In contrast to conventional T cells that recognize peptide antigens presented by major histocompatibility complex...


iNKT Cell Borrelia Burgdorferi Microbial Antigen Lipid Antigen Glycolipid Antigen 
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.



This work was supported by NIH grants R37 AI71922, RO1 AI45053, RO1 AI69276 (MK), and a fellowship from The Irvington Institute Fellowship Program of the Cancer Research Institute Research (Y.K.).


  1. 1.
    Kronenberg, M. (2005)Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23, 877–900CrossRefGoogle Scholar
  2. 2.
    Godfrey, D.I. Berzins, S.P. (2007)Control points in NKT-cell development. Nat Rev Immunol 7, 505–518CrossRefGoogle Scholar
  3. 3.
    Moody, D.B., Zajonc, D.M. Wilson, I.A. (2005)Anatomy of CD1-lipid antigen complexes. Nat Rev Immunol 5, 387–399CrossRefGoogle Scholar
  4. 4.
    Stetson, D.B. et al. (2003)Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198, 1069–1076CrossRefGoogle Scholar
  5. 5.
    Matsuda, J.L. et al. (2003)Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci USA 100, 8395–8400CrossRefGoogle Scholar
  6. 6.
    Brigl, M. Brenner, M.B. (2004)CD1: antigen presentation and T cell function. Annu Rev Immunol 22, 817–890CrossRefGoogle Scholar
  7. 7.
    Kawakami, K. 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, 3322–3330CrossRefGoogle Scholar
  8. 8.
    Nieuwenhuis, E.E. et al. (2002)CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa. from lung Nat Med 8, 588–593CrossRefGoogle Scholar
  9. 9.
    Cui, J. et al. (1997)Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 278, 1623–1626CrossRefGoogle Scholar
  10. 10.
    Joyee, A.G. 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, 1048–1058Google Scholar
  11. 11.
    Tupin, E., Kinjo, Y. Kronenberg, M. (2007)The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 5, 405–417CrossRefGoogle Scholar
  12. 12.
    Ishikawa, H. 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, 1267–1274CrossRefGoogle Scholar
  13. 13.
    Mattner, J., Donhauser, N., Werner-Felmayer, G. Bogdan, C. (2006)NKT cells mediate organ-specific resistance against Leishmania major. infection Microbes Infect 8, 354–362CrossRefGoogle Scholar
  14. 14.
    Amprey, J.L. et al. (2004)A subset of liver NK T cells is activated during Leishmania donovani. infection by CD1d-bound lipophosphoglycan J Exp Med 200, 895–904CrossRefGoogle Scholar
  15. 15.
    Duthie, M.S., Kahn, M., White, M., Kapur, R.P. Kahn, S.J. (2005)Critical proinflammatory and anti-inflammatory functions of different subsets of CD1d-restricted natural killer T cells during Trypanosoma cruzi. infection Infect Immun 73, 181–192CrossRefGoogle Scholar
  16. 16.
    Grubor-Bauk, B., Simmons, A., Mayrhofer, G. Speck, P.G. (2003)Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant V alpha 14-J alpha 281 TCR. J Immunol 170, 1430–1434Google Scholar
  17. 17.
    Ashkar, A.A. Rosenthal, K.L. (2003)Interleukin-15 and natural killer and NKT cells play a critical role in innate protection against genital herpes simplex virus type 2 infection. J Virol 77, 10168–10171CrossRefGoogle Scholar
  18. 18.
    Renukaradhya, G.J. et al. (2005)Virus-induced inhibition of CD1d1-mediated antigen presentation: reciprocal regulation by p38 and ERK. J Immunol 175, 4301–4308Google Scholar
  19. 19.
    Lin, Y., Roberts, T.J., Spence, P.M. Brutkiewicz, R.R. (2005)Reduction in CD1d expression on dendritic cells and macrophages by an acute virus infection. J Leukocyte Biol 77, 151–158CrossRefGoogle Scholar
  20. 20.
    Sanchez, D.J., Gumperz, J.E. Ganem, D. (2005)Regulation of CD1d expression and function by a herpesvirus infection. J Clin Invest 115, 1369–1378Google Scholar
  21. 21.
    Yuan, W., Dasgupta, A. Cresswell, P. (2006)Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling. Nat Immunol 7, 835–842CrossRefGoogle Scholar
  22. 22.
    Chen, N. et al. (2006)HIV-1 down-regulates the expression of CD1d via Nef. Eur J Immunol 36, 278–286CrossRefGoogle Scholar
  23. 23.
    Dieli, F. et al. (2000)Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction. J Exp Med 192, 1645–1652CrossRefGoogle Scholar
  24. 24.
    Nagarajan, N.A. Kronenberg, M. (2007)Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol 178, 2706–2713Google Scholar
  25. 25.
    Nakamatsu, M. et al. (2007)Role of interferon-gamma in Valpha14+natural killer T cell-mediated host defense against Streptococcus pneumoniae. infection in murine lungs Microbes Infect 9, 364–374CrossRefGoogle Scholar
  26. 26.
    Brigl, M., Bry, L., Kent, S.C., Gumperz, J.E. Brenner, M.B. (2003)Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 4, 1230–1237CrossRefGoogle Scholar
  27. 27.
    Mattner, J. et al. (2005)Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525–529CrossRefGoogle Scholar
  28. 28.
    Mallevaey, T. et al. (2006)Activation of invariant NKT cells by the helminth parasite schistosoma mansoni. J Immunol 176, 2476–2485Google Scholar
  29. 29.
    Zhou, D. et al. (2004)Lysosomal glycosphingolipid recognition by NKT cells Science 306, 1786–1789CrossRefGoogle Scholar
  30. 30.
    Gadola, S.D. et al. (2006)Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med 203, 2293–2303CrossRefGoogle Scholar
  31. 31.
    Porubsky, S. 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, 5977–5982CrossRefGoogle Scholar
  32. 32.
    Speak, A.O. 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, 5971–5976CrossRefGoogle Scholar
  33. 33.
    Schofield, L. et al. (1999)CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283, 225–229CrossRefGoogle Scholar
  34. 34.
    Molano, A. 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, 5005–5009Google Scholar
  35. 35.
    Romero, J.F., Eberl, G., MacDonald, H.R. Corradin, G. (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, 267–269CrossRefGoogle Scholar
  36. 36.
    Fischer, K. et al. (2004)Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc Natl Acad Sci USA 101, 10685–10690CrossRefGoogle Scholar
  37. 37.
    Kinjo, Y. et al. (2005)Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434, 520–525CrossRefGoogle Scholar
  38. 38.
    Sriram, V., Du, W., Gervay-Hague, J. Brutkiewicz, R.R. (2005)Cell wall glycosphingolipids of Sphingomonas paucimobilis. are CD1d-specific ligands for NKT cells Eur J Immunol 35, 1692–1701CrossRefGoogle Scholar
  39. 39.
    Neef, A., Witzenberger, R. Kampfer, P. (1999)Detection of sphingomonads and in situ identification in activated sludge using 16S rRNA-targeted oligonucleotide probes. J Ind Microbiol Biotechnol 23, 261–267CrossRefGoogle Scholar
  40. 40.
    Kawahara, K., Kubota, M., Sato, N., Tsuge, K. Seto, Y. (2002)Occurrence of an alpha-galacturonosyl-ceramide in the dioxin-degrading bacterium Sphingomonas wittichii. FEMS Microbiol Lett 214, 289–294Google Scholar
  41. 41.
    Kawahara, K., Moll, H., Knirel, Y.A., Seydel, U. Zahringer, U. (2000)Structural analysis of two glycosphingolipids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata. Eur J Biochem 267, 1837–1846CrossRefGoogle Scholar
  42. 42.
    Hsueh, P.R. et al. (1998)Nosocomial infections caused by Sphingomonas paucimobilis. : clinical features and microbiological characteristics Clin Infect Dis 26, 676–681CrossRefGoogle Scholar
  43. 43.
    Perola, O. et al. (2002)Recurrent Sphingomonas paucimobilis. -bacteraemia associated with a multi-bacterial water-borne epidemic among neutropenic patients J Hosp Infect 50, 196–201CrossRefGoogle Scholar
  44. 44.
    Kumar, H., Belperron, A., Barthold, S.W. Bockenstedt, L.K. (2000)Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J Immunol 165, 4797–4801Google Scholar
  45. 45.
    Ben-Menachem, G., Kubler-Kielb, J., Coxon, B., Yergey, A. Schneerson, R. (2003)A newly discovered cholesteryl galactoside from Borrelia burgdorferi. Proc Natl Acad Sci USA 100, 7913–7918CrossRefGoogle Scholar
  46. 46.
    Kinjo, Y. et al. (2006)Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7, 978–986CrossRefGoogle Scholar
  47. 47.
    Michel, M.L. et al. (2007)Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med 204, 995–1001CrossRefGoogle Scholar
  48. 48.
    Scott-Browne, J.P. et al. (2007)Germline-encoded recognition of diverse glycolipids by natural killer T cells. Nat Immunol 8, 1105–1113CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Yuki Kinjo
    • 1
  • Mitchell Kronenberg
  1. 1.La Jolla Institute for Allergy and ImmunologyLa JollaUSA

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