Neonatology pp 830-847 | Cite as

Fundamentals of Feto-Neonatal Immunology and Its Clinical Relevance

  • Akhil Maheshwari
  • Edmund F. La Gamma


The transition from fetal to neonatal life at birth forms an important functional watershed in the developing immune system. In utero, the fetus is exposed to a steady stream of foreign antigens that are derived mainly from the mother, and must down-regulate its immune response to survive. After birth, however, the neonatal immune system is exposed to a new, more diverse set of antigens and must evolve dichotomous responses to contain the micro-organisms on various cutaneous and mucosal surfaces, and at the same time, develop tolerance to other commensal microbes and dietary macromolecules. During this remarkable transition, while some components of the immune system perform at par with adults, immaturity of the other arms results in a developmentally-regulated state of immunodeficiency. This chapter highlights major quantitative and qualitative differences in the innate and adaptive arms of the neonatal and adult immune systems and provides a brief review of the developing mucosal immune system.


Cord Blood Lamina Propria Preterm Neonate Adult Level Specific Granule 
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. 1.
    Starnes LM, Sorrentino A, Pelosi E et al (2009) NFI-a directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-CSF receptor expression. Blood 114: 1753–1763PubMedCrossRefGoogle Scholar
  2. 2.
    Adamo L, Naveiras O, Wenzel PL S et al (2009) Biomechanical forces promote embryonic haematopoiesis. Nature 459: 1131–1135PubMedCrossRefGoogle Scholar
  3. 3.
    Boxer LA (2006) Severe congenital neutropenia: Genetics and pathogenesis. Trans Am Clin Climatol Assoc 117: 13–31PubMedGoogle Scholar
  4. 4.
    Maheshwari A, Christensen RD (2004) Developmental granulocytopoiesis. In: Polin RA, Fox WW Abman SH (eds), Fetal and neonatal physiology, Vol 2, 3rd edn. WB Saunders Company, Philadelphia, PA, pp 1388–1395Google Scholar
  5. 5.
    Williams DA, Xu H, Cancelas JA (2006) Children are not little adults: Just ask their hematopoietic stem cells. J Clin Invest 116: 2593–2596Google Scholar
  6. 6.
    Christensen RD (1987) Circulating pluripotent hematopoietic progenitor cells in neonates. J Pediatr 110: 623–625PubMedGoogle Scholar
  7. 7.
    Carr R, Huizinga TW (2000) Low soluble FcRIII receptor demonstrates reduced neutrophil reserves in preterm neonates. Arch Dis Child Fetal Neonatal Ed 83: F160PubMedCrossRefGoogle Scholar
  8. 8.
    McIntyre TM, Prescott SM, Weyrich AS, Zimmerman GA (2003) Cell-cell interactions: Leukocyte-endothelial interactions. Curr Opin Hematol 10: 150–158Google Scholar
  9. 9.
    Bagorda A, Mihaylov VA, Parent CA (2006) Chemotaxis: Moving forward and holding on to the past. Thromb Haemost 95: 12–21Google Scholar
  10. 10.
    Shaik SS, Soltau TD, Chaturvedi G et al (2009) Low intensity shear stress increases endothelial elr+ cxc chemokine production via a focal adhesion kinase-p38(beta) mapk-nf-(kappa)b pathway. J Biol Chem 284: 5945–5955PubMedCrossRefGoogle Scholar
  11. 11.
    Rosen SD (2004) Ligands for l-selectin: Homing, inflammation, and beyond. Annu Rev Immunol 22: 129–156PubMedCrossRefGoogle Scholar
  12. 12.
    Edwards SW (1995) Cell signalling by integrins and immunoglobulin receptors in primed neutrophils. Trends Biochem Sci 20: 362–367PubMedCrossRefGoogle Scholar
  13. 13.
    Wagner JG, Roth RA (2000) Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol Rev 52: 349–374PubMedGoogle Scholar
  14. 14.
    Kim SK, Keeney SE, Alpard SK, Schmalstieg FC (2003) Comparison of L-selectin and cd11b on neutrophils of adults and neonates during the first month of life. Pediatr Res 53: 132–136PubMedGoogle Scholar
  15. 15.
    Hashimoto M, Nishida A, Minakami H et al (2002) Decreased expression of L-selectin on peripheral blood polymorphonuclear leukocytes in neonates with severe asphyxia. Biol Neonate 81: 95–98PubMedCrossRefGoogle Scholar
  16. 16.
    Reddy RK, Xia Y, Hanikyrova M, Ross GD (1998) A mixed population of immature and mature leucocytes in umbilical cord blood results in a reduced expression and function of CR3 (CD11B/ CD18). Clin Exp Immunol 114: 462–467PubMedCrossRefGoogle Scholar
  17. 17.
    Linderkamp O, Ruef P, Brenner B et al (1998) Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates. Pediatr Res 44: 946–950PubMedCrossRefGoogle Scholar
  18. 18.
    Heit B, Tavener S, Raharjo E, Kubes P (2002) An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J Cell Biol 159: 91–102PubMedCrossRefGoogle Scholar
  19. 19.
    Bektas S, Goetze B, Speer CP (1990) Decreased adherence, chemotaxis and phagocytic activities of neutrophils from preterm neonates. Acta Paediatr Scand 79: 1031–1038PubMedCrossRefGoogle Scholar
  20. 20.
    Fox SE, Lu W, Maheshwari A et al (2005) The effects and comparative differences of neutrophil specific chemokines on neutrophil chemotaxis of the neonate. Cytokine 29: 135–140PubMedCrossRefGoogle Scholar
  21. 21.
    Sacchi F, Rondini G, Mingrat G et al (1982) Different maturation of neutrophil chemotaxis in term and preterm newborn infants. J Pediatr 101: 273–274PubMedCrossRefGoogle Scholar
  22. 22.
    Eisenfeld L, Krause PJ, Herson V et al (1990) Longitudinal study of neutrophil adherence and motility. J Pediatr 117: 926–929PubMedCrossRefGoogle Scholar
  23. 23.
    Turkmen M, Satar M, Atici A (2000) Neutrophil chemotaxis and random migration in preterm and term infants with sepsis. Am J Perinatol 17: 107–112PubMedCrossRefGoogle Scholar
  24. 24.
    Weinberger B, Laskin DL, Mariano TM et al (2001) Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants. J Leukoc Biol 70: 969–976PubMedGoogle Scholar
  25. 25.
    Krause PJ, Kreutzer DL, Eisenfeld L et al (1989) Characterization of nonmotile neutrophil subpopulations in neonates and adults. Pediatr Res 25: 519–524PubMedCrossRefGoogle Scholar
  26. 26.
    Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23: 197–223PubMedCrossRefGoogle Scholar
  27. 27.
    Carreno MP, Gresham HD, Brown EJ (1993) Isolation of leukocyte response integrin: A novel RGD-binding protein involved in regulation of phagocytic function. Clin Immunol Immunopathol 69: 43–51Google Scholar
  28. 28.
    Etzioni A, Obedeanu N, Blazer S et al (1990) Effect of an intravenous gammaglobulin preparation on the opsonophagocytic activity of preterm serum against coagulase-negative staphylococci. Acta Paediatr Scand 79: 156–161PubMedCrossRefGoogle Scholar
  29. 29.
    Payne NR, Fleit HB (1996) Extremely low birth weight infants have lower Fc gamma RIII (cd 16) plasma levels and their PMN produce less Fc gamma RIII compared to adults. Biol Neonate 69: 235–242PubMedCrossRefGoogle Scholar
  30. 30.
    Payne NR, Frestedt J, Hunkeler N, Gehrz R (1993) Cell-surface expression of immunoglobulin G receptors on the polymorphonuclear leukocytes and monocytes of extremely premature infants. Pediatr Res 33: 452–457PubMedCrossRefGoogle Scholar
  31. 31.
    Quinn MT, Gauss KA (2004) Structure and regulation of the neutrophil respiratory burst oxidase: Comparison with nonphagocyte oxidases. J Leukoc Biol 76: 760–781Google Scholar
  32. 32.
    Clark RA (1999) Activation of the neutrophil respiratory burst oxidase. J Infect Dis 179 Suppl 2: S309–S317CrossRefGoogle Scholar
  33. 33.
    Klebanoff SJ (2005) Myeloperoxidase: Friend and foe. J Leukoc Biol 77: 598–625PubMedCrossRefGoogle Scholar
  34. 34.
    Lehrer RI (2007) Multispecific myeloid defensins. Curr Opin Hematol 14: 16–21PubMedCrossRefGoogle Scholar
  35. 35.
    Moraes TJ, Zurawska JH, Downey GP (2006) Neutrophil granule contents in the pathogenesis of lung injury. Curr Opin Hematol 13: 21–27PubMedCrossRefGoogle Scholar
  36. 36.
    Gahr M, Blanke R, Speer CP (1985) Polymorphonuclear leukocyte function in term and preterm newborn infants. Biol Neonate 48: 15–20PubMedCrossRefGoogle Scholar
  37. 37.
    Komatsu H, Tsukimori K, Hata K et al (2001) The characterization of superoxide production of human neonatal neutrophil. Early Hum Dev 65: 11–19PubMedCrossRefGoogle Scholar
  38. 38.
    Bjorkqvist M, Jurstrand M, Bodin L et al (2004) Defective neutrophil oxidative burst in preterm newborns on exposure to coagulase- negative staphylococci. Pediatr Res 55: 966–971PubMedCrossRefGoogle Scholar
  39. 39.
    Strunk T, Temming P, Gembruch U et al (2004) Differential maturation of the innate immune response in human fetuses. Pediatr Res 56: 219–226PubMedCrossRefGoogle Scholar
  40. 40.
    Borregaard N, Cowland JB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89: 3503–3521PubMedGoogle Scholar
  41. 41.
    Ambruso DR, Bentwood B, Henson PM et al (1984) Oxidative metabolism of cord blood neutrophils: Relationship to content and degranulation of cytoplasmic granules. Pediatr Res 18: 1148–1153Google Scholar
  42. 42.
    Nupponen I, Turunen R, Nevalainen T et al (2002) Extracellular release of bactericidal/permeability-increasing protein in newborn infants. Pediatr Res 51: 670–674PubMedGoogle Scholar
  43. 43.
    Smythies LE, Maheshwari A, Clements R et al (2006) Mucosal IL- 8 and TGF-beta recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells. J Leukoc Biol 80: 492–499PubMedCrossRefGoogle Scholar
  44. 44.
    Maheshwari A, Kurundkar AR, Shaik SS et al (2009) Epithelial cells in fetal intestine produce chemerin to recruit macrophages. Am J Physiol Gastrointest Liver Physiol 297: G1–G10PubMedCrossRefGoogle Scholar
  45. 45.
    Janossy G, Bofill M, Poulter LW et al (1986) Separate ontogeny of two macrophage-like accessory cell populations in the human fetus. J Immunol 136: 4354–4361PubMedGoogle Scholar
  46. 46.
    Kelemen E, Janossa M (1980) Macrophages are the first differentiated blood cells formed in human embryonic liver. Exp Hematol 8: 996–1000PubMedGoogle Scholar
  47. 47.
    Porcellini A, Manna A, Manna M et al (1983) Ontogeny of granulocyte- macrophage progenitor cells in the human fetus. Int J Cell Cloning 1: 92–104PubMedCrossRefGoogle Scholar
  48. 48.
    Linch DC, Knott LJ, Rodeck CH, Huehns ER (1982) Studies of circulating hemopoietic progenitor cells in human fetal blood. Blood 59: 976–979PubMedGoogle Scholar
  49. 49.
    Weinberg AG, Rosenfeld CR, Manroe BL, Browne R (1985) Neonatal blood cell count in health and disease. II. Values for lymphocytes, monocytes, and eosinophils. J Pediatr 106: 462–466Google Scholar
  50. 50.
    Kurland G, Cheung AT, Miller ME et al (1988) The ontogeny of pulmonary defenses: Alveolar macrophage function in neonatal and juvenile rhesus monkeys. Pediatr Res 23: 293–297Google Scholar
  51. 51.
    Johnston RB Jr (1988) Current concepts: Immunology. Monocytes and macrophages. N Engl J Med 318: 747–752PubMedCrossRefGoogle Scholar
  52. 52.
    Yoder MC, Lanker TA, Engle WA (1988) Culture medium oxygen tension affects fibronectin production in human adult and cord blood macrophages. Immunol Lett 19: 1–6PubMedCrossRefGoogle Scholar
  53. 53.
    Bhoopat L, Taylor CR, Hofman FM (1986) The differentiation antigens of macrophages in human fetal liver. Clin Immunol Immunopathol 41: 184–192PubMedCrossRefGoogle Scholar
  54. 54.
    Glover DM, Brownstein D, Burchett S et al (1987) Expression of hla class ii antigens and secretion of interleukin-1 by monocytes and macrophages from adults and neonates. Immunology 61: 195–201PubMedGoogle Scholar
  55. 55.
    Smith PD, Smythies LE, Mosteller-Barnum M et al (2001) Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J Immunol 167: 2651–2656PubMedGoogle Scholar
  56. 56.
    Speer CP, Ambruso DR, Grimsley J, Johnston RB Jr (1985) Oxidative metabolism in cord blood monocytes and monocyte-derived macrophages. Infect Immun 50: 919–921PubMedGoogle Scholar
  57. 57.
    Speer CP, Wieland M, Ulbrich R, Gahr M (1986) Phagocytic activities in neonatal monocytes. Eur J Pediatr 145: 418–421PubMedCrossRefGoogle Scholar
  58. 58.
    D’Ambola JB, Sherman MP, Tashkin DP, Gong H Jr (1988) Human and rabbit newborn lung macrophages have reduced anti-candida activity. Pediatr Res 24: 285–290PubMedCrossRefGoogle Scholar
  59. 59.
    Denning TL, Wang YC, Patel SR et al (2007) Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol 8: 1086–1094PubMedCrossRefGoogle Scholar
  60. 60.
    Smythies LE, Sellers M, Clements RH et al (2005) Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 115: 66–75PubMedGoogle Scholar
  61. 61.
    Weatherstone KB, Rich EA (1989) Tumor necrosis factor/cachectin and interleukin-1 secretion by cord blood monocytes from premature and term neonates. Pediatr Res 25: 342–346PubMedCrossRefGoogle Scholar
  62. 62.
    Bessler H, Sirota L, Dulitzky F, Djaldetti M (1987) Production of interleukin-1 by mononuclear cells of newborns and their mothers. Clin Exp Immunol 68: 655–661PubMedGoogle Scholar
  63. 63.
    Benoit M, Desnues B, Mege JL (2008) Macrophage polarization in bacterial infections. J Immunol 181: 3733–3739PubMedGoogle Scholar
  64. 64.
    Schibler KR, Trautman MS, Liechty KW et al (1993) Diminished transcription of interleukin-8 by monocytes from preterm neonates. J Leukoc Biol 53: 399–403PubMedGoogle Scholar
  65. 65.
    Jaffe R (1993) Review of human dendritic cells: Isolation and culture from precursors. Pediatr Pathol 13: 821–837PubMedCrossRefGoogle Scholar
  66. 66.
    Grouard G, Rissoan MC, Filgueira L et al (1997) The enigmatic plasmacytoid t cells develop into dendritic cells with interleukin (IL)-3 and cd40-ligand. J Exp Med 185: 1101–1111PubMedCrossRefGoogle Scholar
  67. 67.
    Velilla PA, Rugeles MT, Chougnet CA (2006) Defective antigenpresenting cell function in human neonates. Clin Immunol 121: 251–259PubMedCrossRefGoogle Scholar
  68. 68.
    Bondada S, Wu H, Robertson DA, Chelvarajan RL (2000) Accessory cell defect in unresponsiveness of neonates and aged to polysaccharide vaccines. Vaccine 19: 557–565PubMedCrossRefGoogle Scholar
  69. 69.
    Cahill RN, Kimpton WG, Washington EA et al (1999) The ontogeny of T cell recirculation during foetal life. Semin Immunol 11: 105–114PubMedCrossRefGoogle Scholar
  70. 70.
    Haynes BF, Martin ME, Kay HH, Kurtzberg J (1988) Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues. J Exp Med 168: 1061–1080Google Scholar
  71. 71.
    Anderson G, Moore NC, Owen JJ, Jenkinson EJ (1996) Cellular interactions in thymocyte development. Annu Rev Immunol 14: 73–99PubMedCrossRefGoogle Scholar
  72. 72.
    Haynes BF (1984) The human thymic microenvironment. Adv Immunol 36: 87–142PubMedCrossRefGoogle Scholar
  73. 73.
    Bodey B, Kaiser HE (1997) Development of Hassall’s bodies of the thymus in humans and other vertebrates (especially mammals) under physiological and pathological conditions: Immunocytochemical, electronmicroscopic and in vitro observations. In Vivo 11: 61–85Google Scholar
  74. 74.
    Mathieson BJ, Fowlkes BJ (1984) Cell surface antigen expression on thymocytes: Development and phenotypic differentiation of intrathymic subsets. Immunol Rev 82: 141–173Google Scholar
  75. 75.
    Chidgey AP, Boyd RL (2001) Thymic stromal cells and positive selection. APMIS 109: 481–492PubMedCrossRefGoogle Scholar
  76. 76.
    George JF Jr, Schroeder HW Jr (1992) Developmental regulation of d beta reading frame and junctional diversity in t cell receptorbeta transcripts from human thymus. J Immunol 148: 1230–1239PubMedGoogle Scholar
  77. 77.
    Cooper MD, Buckley RH (1982) Developmental immunology and the immunodeficiency diseases. JAMA 248: 2658–2669PubMedCrossRefGoogle Scholar
  78. 78.
    Teyton L, Apostolopoulos V, Cantu C 3rd et al (2000) Function and dysfunction of T cell receptor: Structural studies. Immunol Res 21: 325–330Google Scholar
  79. 79.
    Hazenberg MD, Verschuren MC, Hamann D et al (2001) T cell receptor excision circles as markers for recent thymic emigrants: Basic aspects, technical approach, and guidelines for interpretation. J Mol Med 79: 631–640Google Scholar
  80. 80.
    Oltz EM (2001) Regulation of antigen receptor gene assembly in lymphocytes. Immunol Res 23: 121–133PubMedCrossRefGoogle Scholar
  81. 81.
    Davis MM, Bjorkman PJ (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402PubMedCrossRefGoogle Scholar
  82. 82.
    Schelonka RL, Raaphorst FM, Infante D et al (1998) T cell receptor repertoire diversity and clonal expansion in human neonates. Pediatr Res 43: 396–402PubMedCrossRefGoogle Scholar
  83. 83.
    Garderet L, Dulphy N, Douay C et al (1998) The umbilical cord blood alphabeta T-cell repertoire: Characteristics of a polyclonal and naive but completely formed repertoire. Blood 91: 340–346Google Scholar
  84. 84.
    Erkeller-Yuksel FM, Deneys V, Yuksel B et al (1992) Age-related changes in human blood lymphocyte subpopulations. J Pediatr 120 (2 Part 1): 216–222PubMedGoogle Scholar
  85. 85.
    Series IM, Pichette J, Carrier C et al (1991) Quantitative analysis of T and B cell subsets in healthy and sick premature infants. Early Hum Dev 26: 143–154PubMedCrossRefGoogle Scholar
  86. 86.
    Pirenne H, Aujard Y, Eljaafari A et al (1992) Comparison of t cell functional changes during childhood with the ontogeny of cdw29 and cd45ra expression on cd4+ T cells. Pediatr Res 32: 81–86PubMedCrossRefGoogle Scholar
  87. 87.
    Clerici M, DePalma L, Roilides E et al (1993) Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages. J Clin Invest 91: 2829–2836PubMedCrossRefGoogle Scholar
  88. 88.
    Splawski JB, Jelinek DF, Lipsky PE (1991) Delineation of the functional capacity of human neonatal lymphocytes. J Clin Invest 87: 545–553PubMedCrossRefGoogle Scholar
  89. 89.
    Roncarolo MG, Bigler M, Ciuti E et al (1994) Immune responses by cord blood cells. Blood Cells 20: 573–585PubMedGoogle Scholar
  90. 90.
    Risdon G, Gaddy J, Stehman FB, Broxmeyer HE (1994) Proliferative and cytotoxic responses of human cord blood T lymphocytes following allogeneic stimulation. Cell Immunol 154: 14–24PubMedCrossRefGoogle Scholar
  91. 91.
    Liechty KW, Koenig JM, Mitchell MD et al (1991) Production of interleukin-6 by fetal and maternal cells in vivo during intraamniotic infection and in vitro after stimulation with interleukin-1. Pediatr Res 29: 1–4PubMedCrossRefGoogle Scholar
  92. 92.
    Yachie A, Takano N, Yokoi T et al (1990) The capability of neonatal leukocytes to produce IL-6 on stimulation assessed by whole blood culture. Pediatr Res 27: 227–233PubMedCrossRefGoogle Scholar
  93. 93.
    Seghaye MC, Heyl W, Grabitz RG et al (1998) The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth. Biol Neonate 73: 220–227PubMedCrossRefGoogle Scholar
  94. 94.
    Chheda S, Palkowetz KH, Garofalo R et al (1996) Decreased interleukin- 10 production by neonatal monocytes and t cells: Relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors. Pediatr Res 40: 475–483Google Scholar
  95. 95.
    Qian JX, Lee SM, Suen Y et al (1997) Decreased interleukin-15 from activated cord versus adult peripheral blood mononuclear cells and the effect of interleukin-15 in upregulating antitumor immune activity and cytokine production in cord blood. Blood 90: 3106–3117PubMedGoogle Scholar
  96. 96.
    Lilic D, Cant AJ, Abinun M et al (1997) Cytokine production differs in children and adults. Pediatr Res 42: 237–240PubMedCrossRefGoogle Scholar
  97. 97.
    Chang M, Suen Y, Lee SM et al (1994) Transforming growth factor- beta 1, macrophage inflammatory protein-1 alpha, and interleukin- 8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells. Blood 84: 118–124PubMedGoogle Scholar
  98. 98.
    Cairo MS, Suen Y, Knoppel E et al (1991) Decreased stimulated GM-CSF production and GM-CSF gene expression but normal numbers of GM-CSF receptors in human term newborns compared with adults. Pediatr Res 30: 362–367PubMedCrossRefGoogle Scholar
  99. 99.
    Sullivan SE, Staba SL, Gersting JA et al (2002) Circulating concentrations of chemokines in cord blood, neonates, and adults. Pediatr Res 51: 653–657PubMedCrossRefGoogle Scholar
  100. 100.
    Hagendorens MM, Van Bever HP, Schuerwegh AJ et al (2000) Determination of T-cell subpopulations and intracellular cytokine production (interleukin-2, interleukin-4, and interferon-gamma) by cord blood T-lymphocytes of neonates from atopic and non-atopic parents. Pediatr Allergy Immunol 11: 12–19PubMedCrossRefGoogle Scholar
  101. 101.
    Mosmann TR, Cherwinski H, Bond MW et al (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136: 2348–2357Google Scholar
  102. 102.
    Adkins B (2003) Peripheral cd4+ lymphocytes derived from fetal versus adult thymic precursors differ phenotypically and functionally. J Immunol 171: 5157–5164PubMedGoogle Scholar
  103. 103.
    Weaver CT, Harrington LE, Mangan PR et al (2006) Th17: An effector cd4 T cell lineage with regulatory T cell ties. Immunity 24: 677–688PubMedCrossRefGoogle Scholar
  104. 104.
    Ivanov S, Bozinovski S, Bossios A et al (2007) Functional relevance of the IL-23-IL-17 axis in lungs in vivo. Am J Respir Cell Mol Biol 36: 442–451PubMedCrossRefGoogle Scholar
  105. 105.
    Wilson NJ, Boniface K, Chan JR et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8: 950–957PubMedCrossRefGoogle Scholar
  106. 106.
    Schaub B, Liu J, Schleich I et al (2008) Impairment of T helper and T regulatory cell responses at birth. Allergy 63: 1438–1447PubMedCrossRefGoogle Scholar
  107. 107.
    Takahashi N, Imanishi K, Nishida H, Uchiyama T (1995) Evidence for immunologic immaturity of cord blood T cells. Cord blood T cells are susceptible to tolerance induction to in vitro stimulation with a superantigen. J Immunol 155: 5213–5219Google Scholar
  108. 108.
    Macardle PJ, Wheatland L, Zola H (1999) Analysis of the cord blood T lymphocyte response to superantigen. Hum Immunol 60: 127–139PubMedCrossRefGoogle Scholar
  109. 109.
    Liu CC, Young LH, Young JD (1996) Lymphocyte-mediated cytolysis and disease. N Engl J Med 335: 1651–1659PubMedCrossRefGoogle Scholar
  110. 110.
    Smyth MJ, Kelly JM, Sutton VR et al (2001) Unlocking the secrets of cytotoxic granule proteins. J Leukoc Biol 70: 18–29PubMedGoogle Scholar
  111. 111.
    Toivanen P, Uksila J, Leino A et al (1981) Development of mitogen responding T cells and natural killer cells in the human fetus. Immunol Rev 57: 89–105PubMedCrossRefGoogle Scholar
  112. 112.
    Lubens RG, Gard SE, Soderberg-Warner M, Stiehm ER (1982) Lectin-dependent T-lymphocyte and natural killer cytotoxic deficiencies in human newborns. Cell Immunol 74: 40–53PubMedCrossRefGoogle Scholar
  113. 113.
    McVay LD, Carding SR (1999) Generation of human gammadelta T-cell repertoires. Crit Rev Immunol 19: 431–460PubMedGoogle Scholar
  114. 114.
    Holtmeier W, Pfander M, Hennemann A et al (2001) The TCR-delta repertoire in normal human skin is restricted and distinct from the TCR-delta repertoire in the peripheral blood. J Invest Dermatol 116: 275–280PubMedCrossRefGoogle Scholar
  115. 115.
    Peakman M, Buggins AG, Nicolaides KH et al (1992) Analysis of lymphocyte phenotypes in cord blood from early gestation fetuses. Clin Exp Immunol 90: 345–350PubMedCrossRefGoogle Scholar
  116. 116.
    Morita CT, Parker CM, Brenner MB, Band H (1994) TCR usage and functional capabilities of human gamma delta T cells at birth. J Immunol 153: 3979–3988PubMedGoogle Scholar
  117. 117.
    Sloan-Lancaster J, Allen PM (1996) Altered peptide ligand-induced partial T cell activation: Molecular mechanisms and role in T cell biology. Annu Rev Immunol 14: 1–27Google Scholar
  118. 118.
    Barrat FJ, Cua DJ, Boonstra A et al (2002) In vitro generation of interleukin 10-producing regulatory cd4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 Th1- and Th2-inducing cytokines. J Exp Med 195: 603–616PubMedCrossRefGoogle Scholar
  119. 119.
    Darrasse-Jeze G, Marodon G, Salomon BL et al (2005) Ontogeny of cd4+cd25+ regulatory/suppressor T cells in human fetuses. Blood 105: 4715–4721PubMedCrossRefGoogle Scholar
  120. 120.
    Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor FOXP3. Science 299: 1057–1061PubMedCrossRefGoogle Scholar
  121. 121.
    Klein M (1983) Immunological markers of human mononuclear cells. Clin Biochem 16: 128–133PubMedCrossRefGoogle Scholar
  122. 122.
    Buhl AM, Nemazee D, Cambier JC et al (2000) B-cell antigen receptor competence regulates B-lymphocyte selection and survival. Immunol Rev 176: 141–153PubMedCrossRefGoogle Scholar
  123. 123.
    Rudin CM, Thompson CB (1998) B-cell development and maturation. Semin Oncol 25: 435–446PubMedGoogle Scholar
  124. 124.
    Holt PG, Jones CA (2000) The development of the immune system during pregnancy and early life. Allergy 55: 688–697PubMedCrossRefGoogle Scholar
  125. 125.
    Neuberger MS, Di Noia JM, Beale RC et al (2005) Somatic hypermutation at a.T pairs: Polymerase error versus dutp incorporation. Nat Rev Immunol 5: 171–178Google Scholar
  126. 126.
    Casali P, Schettino EW (1996) Structure and function of natural antibodies. Curr Top Microbiol Immunol 210: 167–179PubMedCrossRefGoogle Scholar
  127. 127.
    Choi Y, Rickert MH, Ballow M, Greenberg SJ (1995) Human IgHv gene repertoire in neonatal cord blood, adult peripheral blood, and EBV-transformed cells. Ann N Y Acad Sci 764: 261–264PubMedCrossRefGoogle Scholar
  128. 128.
    Ridings J, Nicholson IC, Goldsworthy W et al (1997) Somatic hypermutation of immunoglobulin genes in human neonates. Clin Exp Immunol 108: 366–374PubMedCrossRefGoogle Scholar
  129. 129.
    Paloczi K (1999) Immunophenotypic and functional characterization of human umbilical cord blood mononuclear cells. Leukemia 13 (Suppl 1): S87–89PubMedCrossRefGoogle Scholar
  130. 130.
    Ugazio AG, Marcioni AF, Astaldi A Jr, Burgio GR (1974) Peripheral blood B lymphocytes in infancy and childhood. Acta Paediatr Scand 63: 205–208PubMedCrossRefGoogle Scholar
  131. 131.
    Thomas RM, Linch DC (1983) Identification of lymphocyte subsets in the newborn using a variety of monoclonal antibodies. Arch Dis Child 58: 34–38PubMedCrossRefGoogle Scholar
  132. 132.
    Durandy A, Thuillier L, Forveille M, Fischer A (1990) Phenotypic and functional characteristics of human newborns’ B lymphocytes. J Immunol 144: 60–65PubMedGoogle Scholar
  133. 133.
    Johnson CC, Ownby DR, Peterson EL (1996) Parental history of atopic disease and concentration of cord blood IgE. Clin Exp Allergy 26: 624–629PubMedCrossRefGoogle Scholar
  134. 134.
    Sanjeevi CB, Vivekanandan S, Narayanan PR (1991) Fetal response to maternal ascariasis as evidenced by anti ascaris lumbricoides IgM antibodies in the cord blood. Acta Paediatr Scand 80: 1134–1138PubMedCrossRefGoogle Scholar
  135. 135.
    D’Angio CT, Maniscalco WM, Pichichero ME (1995) Immunologic response of extremely premature infants to tetanus, haemophilus influenzae, and polio immunizations. Pediatrics 96 (1 Part 1): 18–22PubMedGoogle Scholar
  136. 136.
    Golebiowska M, Kardas-Sobantka D, Chlebna-Sokol D, Sabanty W (1999) Hepatitis b vaccination in preterm infants. Eur J Pediatr 158: 293–297PubMedCrossRefGoogle Scholar
  137. 137.
    Palfi M, Hilden JO, Gottvall T, Selbing A (1998) Placental transport of maternal immunoglobulin G in pregnancies at risk of Rh (d) hemolytic disease of the newborn. Am J Reprod Immunol 39: 323–328PubMedCrossRefGoogle Scholar
  138. 138.
    Hobbs JR, Davis JA (1967) Serum gamma-G-globulin levels and gestational age in premature babies. Lancet 1: 757–759PubMedCrossRefGoogle Scholar
  139. 139.
    Ballow M, Cates KL, Rowe JC et al (1986) Development of the immune system in very low birth weight (less than 1500 g) premature infants: Concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 20: 899–904Google Scholar
  140. 140.
    Yeung CY, Hobbs JR (1968) Serum-gamma-g-globulin levels in normal premature, post-mature, and “Small-for-dates” Newborn babies. Lancet 1: 1167–1170PubMedCrossRefGoogle Scholar
  141. 141.
    Deorari AK, Broor S, Maitreyi RS et al (2000) Incidence, clinical spectrum, and outcome of intrauterine infections in neonates. J Trop Pediatr 46: 155–159PubMedCrossRefGoogle Scholar
  142. 142.
    Karras JG, Wang Z, Huo L et al (1997) Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes. J Exp Med 185: 1035–1042PubMedCrossRefGoogle Scholar
  143. 143.
    Dorshkind K, Montecino-Rodriguez E (2007) Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nat Rev Immunol 7: 213–219PubMedCrossRefGoogle Scholar
  144. 144.
    Hardy RR (2006) B-1 B cell development. J Immunol 177:2749– 2754Google Scholar
  145. 145.
    Montecino-Rodriguez E, Dorshkind K (2006) New perspectives in B-1 B cell development and function. Trends Immunol 27: 428–433PubMedCrossRefGoogle Scholar
  146. 146.
    Kantor AB, Herzenberg LA (1993) Origin of murine B cell lineages. Annu Rev Immunol 11: 501–538PubMedCrossRefGoogle Scholar
  147. 147.
    Bhat NM, Kantor AB, Bieber MM et al (1992) The ontogeny and functional characteristics of human B-1 (cd5+ B) cells. Int Immunol 4: 243–252PubMedCrossRefGoogle Scholar
  148. 148.
    Hardy RR, Hayakawa K (1991) A developmental switch in B lymphopoiesis. Proc Natl Acad Sci U S A 88: 11550–11554PubMedCrossRefGoogle Scholar
  149. 149.
    Alugupalli KR, Leong JM, Woodland RT et al (2004) B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity 21: 379–390PubMedCrossRefGoogle Scholar
  150. 150.
    Haas KM, Poe JC, Steeber DA, Tedder TF (2005) B-1a and B-1B cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. Pneumoniae. Immunity 23: 7–18Google Scholar
  151. 151.
    Bishop GA, Hostager BS (2001) B lymphocyte activation by contact- mediated interactions with T lymphocytes. Curr Opin Immunol 13: 278–285PubMedCrossRefGoogle Scholar
  152. 152.
    Nonoyama S, Etzioni A, Toru H et al (1998) Diminished expression of cd40 ligand may contribute to the defective humoral immunity in patients with MHC class II deficiency. Eur J Immunol 28: 589–598PubMedCrossRefGoogle Scholar
  153. 153.
    Merrill JD, Sigaroudinia M, Kohl S (1996) Characterization of natural killer and antibody-dependent cellular cytotoxicity of preterm infants against human immunodeficiency virus-infected cells. Pediatr Res 40: 498–503PubMedCrossRefGoogle Scholar
  154. 154.
    Splawski JB, Nishioka J, Nishioka Y, Lipsky PE (1996) Cd40 ligand is expressed and functional on activated neonatal t cells. J Immunol 156: 119–127PubMedGoogle Scholar
  155. 155.
    Lucivero G, Dell’Osso A, Iannone A et al (1983) Phenotypic immaturity of T and B lymphocytes in cord blood of full-term normal neonates. Analysis of cell surface markers by using conventional techniques and monoclonal antibodies. Biol Neonate 44: 303–308Google Scholar
  156. 156.
    Spits H, Lanier LL, Phillips JH (1995) Development of human T and natural killer cells. Blood 85: 2654–2670PubMedGoogle Scholar
  157. 157.
    Puel A, Ziegler SF, Buckley RH, Leonard WJ (1998) Defective IL7R expression in t(-)b(+)nk(+) severe combined immunodeficiency. Nat Genet 20: 394–397PubMedCrossRefGoogle Scholar
  158. 158.
    Volpe R (1996) Graves’ disease/model of scid mouse. Exp Clin Endocrinol Diabetes 104 (Suppl 3): 37–40PubMedCrossRefGoogle Scholar
  159. 159.
    Phillips JH, Hori T, Nagler A et al (1992) Ontogeny of human natural killer (NK) cells: Fetal NK cells mediate cytolytic function and express cytoplasmic cd3 epsilon, delta proteins. J Exp Med 175: 1055–1066PubMedCrossRefGoogle Scholar
  160. 160.
    Sato T, Laver JH, Aiba Y, Ogawa M (1999) NK cell colony formation from human fetal thymocytes. Exp Hematol 27: 726–733PubMedCrossRefGoogle Scholar
  161. 161.
    Spits H, Blom B, Jaleco AC et al (1998) Early stages in the development of human T, natural killer and thymic dendritic cells. Immunol Rev 165: 75–86PubMedCrossRefGoogle Scholar
  162. 162.
    Gaddy J, Risdon G, Broxmeyer HE (1995) Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12. J Interferon Cytokine Res 15: 527–536PubMedCrossRefGoogle Scholar
  163. 163.
    Leibson PJ (1997) Signal transduction during natural killer cell activation: Inside the mind of a killer. Immunity 6: 655–661PubMedCrossRefGoogle Scholar
  164. 164.
    Ortaldo JR, Winkler-Pickett RT, Nagashima K et al (1992) Direct evidence for release of pore-forming protein during nk cellular lysis. J Leukoc Biol 52: 483–488PubMedGoogle Scholar
  165. 165.
    Trinchieri G, Valiante N (1993) Receptors for the Fc fragment of IgG on natural killer cells. Nat Immun 12: 218–234PubMedGoogle Scholar
  166. 166.
    Gaunt G, Ramin K (2001) Immunological tolerance of the human fetus. Am J Perinatol 18: 299–312PubMedCrossRefGoogle Scholar
  167. 167.
    Middendorp S, Nieuwenhuis EE (2009) NKT cells in mucosal immunity. Mucosal Immunol 2: 393 - 402PubMedCrossRefGoogle Scholar
  168. 168.
    Finke D, Acha-Orbea H, Mattis A et al (2002) Cd4+cd3- cells induce Peyer’s patch development: Role of alpha4beta1 integrin activation by CXCR5. Immunity 17: 363–373PubMedCrossRefGoogle Scholar
  169. 169.
    Spencer J, Finn T, Isaacson PG (1985) Gut associated lymphoid tissue: A morphological and immunocytochemical study of the human appendix. Gut 26: 672–679Google Scholar
  170. 170.
    MacDonald TT, Spencer J (1994) Ontogeny of the gut-associated lymphoid system in man. Acta Paediatr Suppl 83: 3–5PubMedCrossRefGoogle Scholar
  171. 171.
    Husband AJ, Gleeson M (1996) Ontogeny of mucosal immunityenvironmental and behavioral influences. Brain Behav Immun 10: 188–204PubMedCrossRefGoogle Scholar
  172. 172.
    Cornes JS (1965) Peyer’s patches in the human gut. Proc R Soc Med 58: 716PubMedGoogle Scholar
  173. 173.
    Bhide SA, Wadekar KV, Koushik SA (2001) Peyer’s patches are precocious to the appendix in human development. Dev Immunol 8: 159–166PubMedCrossRefGoogle Scholar
  174. 174.
    Gebbers JO, Laissue JA (2004) Bacterial translocation in the normal human appendix parallels the development of the local immune system. Ann N Y Acad Sci 1029: 337–343PubMedCrossRefGoogle Scholar
  175. 175.
    Golby S, Hackett M, Boursier L et al (2002) B cell development and proliferation of mature B cells in human fetal intestine. J Leukoc Biol 72: 279–284PubMedGoogle Scholar
  176. 176.
    Rognum TO, Thrane S, Stoltenberg L et al (1992) Development of intestinal mucosal immunity in fetal life and the first postnatal months. Pediatr Res 32: 145–149PubMedCrossRefGoogle Scholar
  177. 177.
    Fagarasan S, Kinoshita K, Muramatsu M et al (2001) In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413: 639–643PubMedCrossRefGoogle Scholar
  178. 178.
    Shroff KE, Meslin K, Cebra JJ (1995) Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect Immun 63: 3904–3913PubMedGoogle Scholar
  179. 179.
    Spencer J, MacDonald TT, Finn T, Isaacson PG (1986) The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine. Clin Exp Immunol 64: 536–543PubMedGoogle Scholar
  180. 180.
    Cerf-Bensussan N, Guy-Grand D (1991) Intestinal intraepithelial lymphocytes. Gastroenterol Clin North Am 20: 549–576PubMedGoogle Scholar
  181. 181.
    Gunther U, Holloway JA, Gordon JN et al (2005) Phenotypic characterization of cd3-7+ cells in developing human intestine and an analysis of their ability to differentiate into T cells. J Immunol 174: 5414–5422PubMedGoogle Scholar
  182. 182.
    Williams AM, Bland PW, Phillips AC et al (2004) Intestinal alpha beta T cells differentiate and rearrange antigen receptor genes in situ in the human infant. J Immunol 173: 7190–7199PubMedGoogle Scholar
  183. 183.
    Boismenu R, Havran WL (1994) Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science 266: 1253–1255PubMedCrossRefGoogle Scholar
  184. 184.
    Kagnoff MF (1998) Current concepts in mucosal immunity. III. Ontogeny and function of gamma delta T cells in the intestine. Am J Physiol 274 (3 Part 1): G455–G458PubMedGoogle Scholar
  185. 185.
    Holtmeier W, Witthoft T, Hennemann A et al (1997) The TCR-delta repertoire in human intestine undergoes characteristic changes during fetal to adult development. J Immunol 158: 5632–5641PubMedGoogle Scholar
  186. 186.
    Haworth JC, Dilling L (1966) Concentration of gamma-A-globulin in serum, saliva, and nasopharyngeal secretions of infants and children. J Lab Clin Med 67: 922–933PubMedGoogle Scholar
  187. 187.
    Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS (1991) Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am 20: 397–439PubMedGoogle Scholar
  188. 188.
    Gleeson M, Cripps AW, Clancy RL et al (1982) Ontogeny of the secretory immune system in man. Aust N Z J Med 12: 255–258PubMedCrossRefGoogle Scholar
  189. 189.
    Mellander L, Carlsson B, Hanson LA (1984) Appearance of secretory IgM and IgA antibodies to escherichia coli in saliva during early infancy and childhood. J Pediatr 104: 564–568PubMedCrossRefGoogle Scholar
  190. 190.
    Hayes JA, Adamson-Macedo EN, Perera S, Anderson J (1999) Detection of secretory immunoglobulin A ( SIgA) in saliva of ventilated and non-ventilated preterm neonates. Neuroendocrinol Lett 20: 109–113Google Scholar
  191. 191.
    Wan AK, Seow WK, Purdie DM et al (2003) Immunoglobulins in saliva of preterm and full-term infants. Oral Microbiol Immunol 18: 72–78PubMedCrossRefGoogle Scholar
  192. 192.
    Fitzsimmons SP, Evans MK, Pearce CL et al (1994) Immunoglobulin a subclasses in infants’ saliva and in saliva and milk from their mothers. J Pediatr 124: 566–573PubMedCrossRefGoogle Scholar
  193. 193.
    Burgio GR, Lanzavecchia A, Plebani A et al (1980) Ontogeny of secretory immunity: Levels of secretory IgA and natural antibodies in saliva. Pediatr Res 14: 1111–1114Google Scholar
  194. 194.
    Cripps AW, Gleeson M, Clancy RL (1991) Ontogeny of the mucosal immune response in children. Adv Exp Med Biol 310: 87–92PubMedCrossRefGoogle Scholar
  195. 195.
    Weemaes C, Klasen I, Goertz J et al (2003) Development of immunoglobulin A in infancy and childhood. Scand J Immunol 58: 642–648PubMedCrossRefGoogle Scholar
  196. 196.
    Lodinova R, Jouja V, Wagner V (1973) Serum immunoglobulins and coproantibody formation in infants after artificial intestinal colonization with escherichia coli 083 and oral lysozyme administration. Pediatr Res 7: 659–669PubMedCrossRefGoogle Scholar
  197. 197.
    Onyemelukwe GC, Leinoen M, Makela H, Greenwood BM (1985) Response to pneumococcal vaccination in normal and post-infected nigerians. J Infect 11: 139–144PubMedCrossRefGoogle Scholar
  198. 198.
    Ogra PL, Losonsky GA, Fishaut M (1983) Colostrum-derived immunity and maternal-neonatal interaction. Ann N Y Acad Sci 409: 82–95PubMedCrossRefGoogle Scholar
  199. 199.
    Hanson LA, Korotkova M (2002) The role of breastfeeding in prevention of neonatal infection. Semin Neonatol 7: 275–281PubMedGoogle Scholar
  200. 200.
    Takahashi T, Yoshida Y, Hatano S et al (2002) Reactivity of secretory IgA antibodies in breast milk from 107 Japanese mothers to 20 environmental antigens. Biol Neonate 82: 238–242PubMedCrossRefGoogle Scholar
  201. 201.
    Araujo ED, Goncalves AK, Cornetta Mda C et al (2005) Evaluation of the secretory immunoglobulin a levels in the colostrum and milk of mothers of term and pre-trerm newborns. Braz J Infect Dis 9: 357–362PubMedGoogle Scholar
  202. 202.
    Mayer L (2005) Mucosal immunity. Immunol Rev 206: 5PubMedCrossRefGoogle Scholar
  203. 203.
    Chen ZJ, Wheeler CJ, Shi W et al (1998) Polyreactive antigenbinding B cells are the predominant cell type in the newborn B cell repertoire. Eur J Immunol 28: 989–994PubMedCrossRefGoogle Scholar
  204. 204.
    Bauer K, Zemlin M, Hummel M et al (2002) Diversification of Ig heavy chain genes in human preterm neonates prematurely exposed to environmental antigens. J Immunol 169: 1349–1356PubMedGoogle Scholar
  205. 205.
    Collis AV, Brouwer AP, Martin AC (2003) Analysis of the antigen combining site: Correlations between length and sequence composition of the hypervariable loops and the nature of the antigen. J Mol Biol 325: 337–354Google Scholar
  206. 206.
    Zemlin M, Bauer K, Hummel M et al (2001) The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage. Blood 97: 1511–1513PubMedCrossRefGoogle Scholar
  207. 207.
    Collins AM, Sewell WA, Edwards MR (2003) Immunoglobulin gene rearrangement, repertoire diversity, and the allergic response. Pharmacol Ther 100: 157–170PubMedCrossRefGoogle Scholar
  208. 208.
    Maheshwari A, Zemlin M (2006) Ontogeny of the intestinal immune system. Haematologica Reports 10: 18–26Google Scholar
  209. 209.
    Braegger CP, Spencer J, MacDonald TT (1992) Ontogenetic aspects of the intestinal immune system in man. Int J Clin Lab Res 22: 1–4PubMedCrossRefGoogle Scholar
  210. 210.
    Smythies LE, Maheshwari A, Clements R et al (2006) Mucosal IL- 8 and TGF-beta recruit blood monocytes: Evidence for cross-talk between the lamina propria stroma and myeloid cells. J Leukoc Biol 80: 492–499Google Scholar
  211. 211.
    van Elburg RM, Fetter WP, Bunkers CM, Heymans HS (2003) Intestinal permeability in relation to birth weight and gestational and postnatal age. Arch Dis Child Fetal Neonatal Ed 88: F52–F55PubMedCrossRefGoogle Scholar
  212. 212.
    Kelsall B (2008) Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages. Mucosal Immunol 1: 460–469PubMedCrossRefGoogle Scholar
  213. 213.
    Maheshwari A, Voitenok NN, Akalovich S et al (2009) Developmental changes in circulating IL-8/CXCL8 isoforms in neonates. Cytokine 46: 12–16PubMedCrossRefGoogle Scholar
  214. 214.
    Adams DH, Hathaway M, Shaw J et al (1991) Transforming growth factor-beta induces human T lymphocyte migration in vitro. J Immunol 147: 609–612PubMedGoogle Scholar
  215. 215.
    MacDonald TT (1996) Accessory cells in the human gastrointestinal tract. Histopathology 29: 89–92PubMedCrossRefGoogle Scholar
  216. 216.
    Makori N, Tarantal AF, Lu FX et al (2003) Functional and morphological development of lymphoid tissues and immune regulatory and effector function in rhesus monkeys: Cytokine-secreting cells, immunoglobulin-secreting cells, and cd5(+) B-1 cells appear early in fetal development. Clin Diagn Lab Immunol 10: 140–153PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Akhil Maheshwari
    • 1
  • Edmund F. La Gamma
  1. 1.Division of Neonatology, Children’s HospitalUniversity of Illinois at ChicagoChicagoUSA

Personalised recommendations