Advertisement

Seminars in Immunopathology

, Volume 39, Issue 6, pp 585–592 | Cite as

In utero development of memory T cells

  • Dania Zhivaki
  • Richard Lo-ManEmail author
Review

Abstract

Pathogen-specific immune memory develops subsequent to primary exposure to antigen, mainly in the context of infection or vaccination to provide protection. Although a safe fetal life requires a tolerogenic environment in order to circumvent unnecessary inflammatory responses, it needs to be prepared in utero to face the microbial environment outside the womb. The possibility of immune memory generation in the fetus would help such transition providing protection in early life. This requires fetal T cell exposure to foreign antigens presented by dendritic cells. There are evidences of fetal T cell priming in several cases of congenital infections or in uninfected children born of infected mothers. Fetal T cell memory seems to arise also without any reported infection during pregnancy. Such memory T cells display various effector functions, including Th1, Th2, or Th17 profiles, raising the issue of benefits and risks for postnatal life when considering maternal vaccination, susceptibility to infection, or environmental allergen sensitization.

Keywords

Fetus T cell Immune memory 

Notes

Acknowledgements

We thank Dr. Laleh Majlessi for critically revising the MS.

Funding information

RLM is supported by an ANR grant (ANR 13-BSV3-0016) and by the Fondation pour la Recherche Médicale (grant no. DEQ20120323719). This study also received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID).

References

  1. 1.
    Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7(9):715–725CrossRefPubMedGoogle Scholar
  2. 2.
    PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O, Siegrist C-A (2011) Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol 12:189–194CrossRefPubMedGoogle Scholar
  3. 3.
    Siegrist CA (2001) Neonatal and early life vaccinology. Vaccine 19(25–26):3331–3346CrossRefPubMedGoogle Scholar
  4. 4.
    Vekemans J, Amedei A, Ota MO, D'Elios MM, Goetghebuer T, Ismaili J, Newport MJ, Del Prete G, Goldman M, McAdam KP, Marchant A (2001) Neonatal bacillus Calmette-Guérin vaccination induces adult-like IFN-gamma production by CD4+ T lymphocytes. Eur J Immunol 31:1531–1535CrossRefPubMedGoogle Scholar
  5. 5.
    Corbett NP, Blimkie D, Ho KC, Cai B, Sutherland DP, Kallos A, Crabtree J, Rein-Weston A, Lavoie PM, Turvey SE, Hawkins NR, Self SG, Wilson CB, Hajjar AM, Fortuno ES 3rd, Kollmann TR (2010) Ontogeny of Toll-like receptor mediated cytokine responses of human blood mononuclear cells. PLoS One 5(11):e15041CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Marchant EA, Kan B, Sharma AA, van Zanten A, Kollmann TR, Brant R, Lavoie PM (2015) Attenuated innate immune defenses in very premature neonates during the neonatal period. Pediatr Res 78(5):492–497CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Griffin DO, Holodick NE, Rothstein TL (2011) Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+ CD43+ CD70−. J Exp Med 208:67–80CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhivaki D, Lemoine S, Lim A, Morva A, Vidalain PO, Schandene L, Casartelli N, Rameix-Welti MA, Herve PL, Deriaud E, Beitz B, Ripaux-Lefevre M, Miatello J, Lemercier B, Lorin V, Descamps D, Fix J, Eleouet JF, Riffault S, Schwartz O, Porcheray F, Mascart F, Mouquet H, Zhang X, Tissieres P, Lo-Man R (2017) Respiratory syncytial virus infects regulatory B cells in human neonates via chemokine receptor CX3CR1 and promotes lung disease severity. Immunity 46(2):301–314CrossRefPubMedGoogle Scholar
  9. 9.
    Kurosaki T, Kometani K, Ise W (2015) Memory B cells. Nat Rev Immunol 15(3):149–159CrossRefPubMedGoogle Scholar
  10. 10.
    Krow-Lucal ER, Kim CC, Burt TD, McCune JM (2014) Distinct functional programming of human fetal and adult monocytes. Blood 123(12):1897–1904CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mold JE, McCune JM (2011) At the crossroads between tolerance and aggression: revisiting the “layered immune system” hypothesis. Chimerism 2(2):35–41CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sprent J, Surh CD (2011) Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells. Nat Immunol 12(6):478–484CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bunders MJ, van der Loos CM, Klarenbeek PL, van Hamme JL, Boer K, Wilde JCH, de Vries N, van Lier RAW, Kootstra N, Pals ST, Kuijpers TW (2012) Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1. Blood 120:4383–4390CrossRefPubMedGoogle Scholar
  14. 14.
    Byrne JA, Stankovic AK, Cooper MD (1994) A novel subpopulation of primed T cells in the human fetus. J Immunol 152(6):3098–3106PubMedGoogle Scholar
  15. 15.
    Crespo M, Martinez DG, Cerissi A, Rivera-Reyes B, Bernstein HB, Lederman MM, Sieg SF, Luciano AA (2012) Neonatal T-cell maturation and homing receptor responses to Toll-like receptor ligands differ from those of adult naive T cells: relationship to prematurity. Pediatr Res 71:136CrossRefPubMedGoogle Scholar
  16. 16.
    Dobber R, Hertogh-Huijbregts A, Rozing J, Bottomly K, Nagelkerken L (1992) The involvement of the intestinal microflora in the expansion of CD4+ T cells with a naive phenotype in the periphery. Dev Immunol 2:141–150CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vos Q, Jones LA, Kruisbeek AM (1992) Mice deprived of exogenous antigenic stimulation develop a normal repertoire of functional T cells. J Immunol (Baltimore, Md : 1950) 149:1204–1210Google Scholar
  18. 18.
    Schuster C, Vaculik C, Fiala C, Meindl S, Brandt O, Imhof M, Stingl G, Eppel W, Elbe-Burger A (2009) HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells. J Exp Med 206(1):169–181CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    McGovern N, Shin A, Low G, Low D, Duan K, Yao LJ, Msallam R, Low I, Shadan NB, Sumatoh HR, Soon E, Lum J, Mok E, Hubert S, See P, Kunxiang EH, Lee YH, Janela B, Choolani M, Mattar CNZ, Fan Y, Lim TKH, Chan DKH, Tan KK, Tam JKC, Schuster C, Elbe-Burger A, Wang XN, Bigley V, Collin M, Haniffa M, Schlitzer A, Poidinger M, Albani S, Larbi A, Newell EW, Chan JKY, Ginhoux F (2017) Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature 546(7660):662–666CrossRefPubMedGoogle Scholar
  20. 20.
    Le Campion A, Bourgeois C, Lambolez F, Martin B, Leaument S, Dautigny N, Tanchot C, Penit C, Lucas B (2002) Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes. Proc Natl Acad Sci U S A 99(7):4538–4543CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Haddad R, Guimiot F, Six E, Jourquin F, Setterblad N, Kahn E, Yagello M, Schiffer C, Andre-Schmutz I, Cavazzana-Calvo M, Gluckman JC, Delezoide A-L, Pflumio F, Canque B (2006) Dynamics of thymus-colonizing cells during human development. Immunity 24:217–230CrossRefPubMedGoogle Scholar
  22. 22.
    Haynes BF, Heinly CS (1995) Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment. J Exp Med 181:1445–1458CrossRefPubMedGoogle Scholar
  23. 23.
    Lobach DF, Hensley LL, Ho W, Haynes BF (1985) Human T cell antigen expression during the early stages of fetal thymic maturation. J Immunol 135:1752–1759PubMedGoogle Scholar
  24. 24.
    Starr TK, Jameson SC, Hogquist KA (2003) Positive and negative selection of T cells. Annu Rev Immunol 21:139–176CrossRefPubMedGoogle Scholar
  25. 25.
    Hsieh CS, Lee HM, Lio CW (2012) Selection of regulatory T cells in the thymus. Nat Rev Immunol 12(3):157–167PubMedGoogle Scholar
  26. 26.
    Haynes BF, Hale LP (1998) The human thymus. A chimeric organ comprised of central and peripheral lymphoid components. Immunol Res 18:175–192CrossRefPubMedGoogle Scholar
  27. 27.
    Rechavi E, Lev A, Lee YN, Simon AJ, Yinon Y, Lipitz S, Amariglio N, Weisz B, Notarangelo LD, Somech R (2015) Timely and spatially regulated maturation of B and T cell repertoire during human fetal development. Sci Transl Med 7(276):276ra25CrossRefPubMedGoogle Scholar
  28. 28.
    Mold JE, McCune JM (2012) Immunological tolerance during fetal development: from mouse to man. In: Alt FW (ed) Advances in immunology, Vol 115. Elsevier Academic Press Inc, San Diego, pp 73–111Google Scholar
  29. 29.
    Erlebacher A (2012) Mechanisms of T cell tolerance towards the allogeneic fetus. Nat Rev Immunol 13:23–33CrossRefPubMedGoogle Scholar
  30. 30.
    Rowe JH, Ertelt JM, Xin L, Way SS (2012) Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 490(7418):102–106CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kinder JM, Jiang TT, Ertelt JM, Xin L, Strong BS, Shaaban AF, Way SS (2015) Cross-generational reproductive fitness enforced by microchimeric maternal cells. Cell 162(3):505–515CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rosenblum MD, Way SS, Abbas AK (2015) Regulatory T cell memory. Nat Rev Immunol 16:90–101CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mold JE, Michaëlsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee T-H, Nixon DF, McCune JM (2008) Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science (New York, NY) 322:1562–1565CrossRefGoogle Scholar
  34. 34.
    Mold JE, Venkatasubrahmanyam S, Burt TD, Michaëlsson J, Rivera JM, Galkina SA, Weinberg K, Stoddart CA, McCune JM (2010) Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans. Science (New York, NY) 330:1695–1699CrossRefGoogle Scholar
  35. 35.
    Tsafrir A, Brautbar C, Nagler A, Elchalal U, Miller K, Bishara A (2000) Alloreactivity of umbilical cord blood mononuclear cells: specific hyporesponse to noninherited maternal antigens. Hum Immunol 61(6):548–554CrossRefPubMedGoogle Scholar
  36. 36.
    Bailey-Bucktrout SL, Martinez-Llordella M, Zhou X, Anthony B, Rosenthal W, Luche H, Fehling HJ, Bluestone JA (2013) Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity 39:949–962CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Zhou X, Bailey-Bucktrout SL, Jeker LT, Penaranda C, Martínez-Llordella M, Ashby M, Nakayama M, Rosenthal W, Bluestone JA (2009) Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol 10:1000–1007CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Takahashi R, Nishimoto S, Muto G, Sekiya T, Tamiya T, Kimura A, Morita R, Asakawa M, Chinen T, Yoshimura A (2011) SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production. J Exp Med 208:2055–2067CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    McClymont SA, Putnam AL, Lee MR, Esensten JH, Liu W, Hulme MA, Hoffmuller U, Baron U, Olek S, Bluestone JA, Brusko TM (2011) Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J Immunol 186:3918–3926CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Dominguez-Villar M, Baecher-Allan CM, Hafler DA (2011) Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nat Med 17:673–675CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Smith M, Tourigny MR, Noakes P, Catherine A, Tulic MK, Prescott SL (2008) Children with egg allergy have evidence of reduced neonatal CD4(+)CD25(+)CD127(lo/−) regulatory T cell function. J Allergy Clin Immunol 121(6):1460–1466CrossRefPubMedGoogle Scholar
  42. 42.
    Schaub B, Liu J, Hoppler S, Haug S, Sattler C, Lluis A, Illi S, von Mutius E (2008) Impairment of T-regulatory cells in cord blood of atopic mothers. J Allergy Clin Immunol 121(6):1491–1499CrossRefPubMedGoogle Scholar
  43. 43.
    Zhang Y, Collier F, Naselli G, Saffery R, Tang ML, Allen KJ, Ponsonby AL, Harrison LC, Vuillermin P, B.I.S.I. Group (2016) Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic “T(H)2-type” immunity associated with development of food allergy. Sci Transl Med 8(321):321ra8CrossRefPubMedGoogle Scholar
  44. 44.
    Trowbridge IS, Thomas ML (1994) CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu Rev Immunol 12:85–116CrossRefPubMedGoogle Scholar
  45. 45.
    Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712CrossRefPubMedGoogle Scholar
  46. 46.
    Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C, Wang E, Douek DC, Price DA, June CH, Marincola FM, Roederer M, Restifo NP (2011) A human memory T cell subset with stem cell-like properties. Nat Med 17(10):1290–1297CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, Roychoudhuri R, Ferreyra GA, Shen W, Durum SK, Feigenbaum L, Palmer DC, Antony PA, Chan CC, Laurence A, Danner RL, Gattinoni L, Restifo NP (2011) Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity 35(6):972–985CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Takeshita M, Suzuki K, Kassai Y, Takiguchi M, Nakayama Y, Otomo Y, Morita R, Miyazaki T, Yoshimura A, Takeuchi T (2015) Polarization diversity of human CD4+ stem cell memory T cells. Clin Immunol 159(1):107–117CrossRefPubMedGoogle Scholar
  49. 49.
    Luciano AA, Yu H, Jackson LW, Wolfe LA, Bernstein HB (2011) Preterm labor and chorioamnionitis are associated with neonatal T cell activation. PLoS One 6:e16698CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Schuster C, Vaculik C, Prior M, Fiala C, Mildner M, Eppel W, Stingl G, Elbe-Bürger A (2012) Phenotypic characterization of leukocytes in prenatal human dermis. J Invest Dermatol 132(11):2581–2592CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10(7):490–500CrossRefPubMedGoogle Scholar
  52. 52.
    van Der Vliet HJ, Nishi N, de Gruijl TD, von Blomberg BM, van den Eertwegh AJ, Pinedo HM, Giaccone G, Scheper RJ (2000) Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95(7):2440–2442Google Scholar
  53. 53.
    Kadowaki N, Antonenko S, Ho S, Rissoan MC, Soumelis V, Porcelli SA, Lanier LL, Liu YJ (2001) Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells. J Exp Med 193(10):1221–1226CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, Lester C, Besra G, Vomhof-Dekrey EE, Tighe M, Koay HF, Godfrey DI, Leadbetter EA, Sant'Angelo DB, von Andrian U, Brenner MB (2015) Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol 16(1):85–95CrossRefPubMedGoogle Scholar
  55. 55.
    Leeansyah E, Loh L, Nixon DF, Sandberg JK (2014) Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development. Nat Commun 5:3143CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Michaelsson J, Mold JE, McCune JM, Nixon DF (2006) Regulation of T cell responses in the developing human fetus. J Immunol 176(10):5741–5748CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang X, Mozeleski B, Lemoine S, Deriaud E, Lim A, Zhivaki D, Azria E, Le Ray C, Roguet G, Launay O, Vanet A, Leclerc C, Lo-Man R (2014) CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus. Sci Transl Med 6:238ra72–238ra72CrossRefPubMedGoogle Scholar
  58. 58.
    Cosmi L, Annunziato F, MIG G, RME M, Nagata K, Romagnani S (2000) CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol 30:2972–2979CrossRefPubMedGoogle Scholar
  59. 59.
    Jameson SC, Lee YJ, Hogquist KA (2015) Innate memory T cells. Adv Immunol 126:173–213CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Jacomet F, Cayssials E, Basbous S, Levescot A, Piccirilli N, Desmier D, Robin A, Barra A, Giraud C, Guilhot F, Roy L, Herbelin A, Gombert JM (2015) Evidence for eomesodermin-expressing innate-like CD8(+) KIR/NKG2A(+) T cells in human adults and cord blood samples. Eur J Immunol 45(7):1926–1933CrossRefPubMedGoogle Scholar
  61. 61.
    White JT, Cross EW, Kedl RM (2017) Antigen-inexperienced memory CD8+ T cells: where they come from and why we need them. Nat Rev Immunol 17(6):391–400CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Gerdts V, Babiuk LA, van den Drunen Littel-van H, Griebel PJ (2000) Fetal immunization by a DNA vaccine delivered into the oral cavity. Nat Med 6(8):929–932CrossRefPubMedGoogle Scholar
  63. 63.
    Aase JM, Noren GR, Reddy DV, Geme JW Jr (1972) Mumps-virus infection in pregnant women and the immunologic response of their offspring. N Engl J Med 286(26):1379–1382CrossRefPubMedGoogle Scholar
  64. 64.
    Marchant A, Appay V, Van Der Sande M, Dulphy N, Liesnard C, Kidd M, Kaye S, Ojuola O, Gillespie GMA, Vargas Cuero AL, Cerundolo V, Callan M, McAdam KPWJ, Rowland-Jones SL, Donner C, McMichael AJ, Whittle H (2003) Mature CD8(+) T lymphocyte response to viral infection during fetal life. J Clin Invest 111:1747–1755CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Miles DJC, van Sande MD, Kaye S, Crozier S, Ojuola O, Palmero MS, Sanneh M, Touray ES, Waight P, Rowland-Jones S, Whittle H, Marchant A (2008) CD4 T cell responses to cytomegalovirus in early life: a prospective birth cohort study. J Infect Dis 197:658–662CrossRefPubMedGoogle Scholar
  66. 66.
    Rowland-Jones SL, Nixon DF, Aldhous MC, Gotch F, Ariyoshi K, Hallam N, Kroll JS, Froebel K, McMichael A (1993) HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. Lancet 341(8849):860–861CrossRefPubMedGoogle Scholar
  67. 67.
    Koumbi L, Bertoletti A, Anastasiadou V, Machaira M, Goh W, Papadopoulos NG, Kafetzis DA, Papaevangelou V (2010) Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg- mothers. Cell Mol Immunol 7(6):454–458CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Babik JM, Cohan D, Monto A, Hartigan-O'Connor DJ, McCune JM (2011) The human fetal immune response to hepatitis C virus exposure in utero. J Infect Dis 203(2):196–206CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Metenou S, Suguitan AL Jr, Long C, Leke RG, Taylor DW (2007) Fetal immune responses to Plasmodium falciparum antigens in a malaria-endemic region of Cameroon. J Immunol 178(5):2770–2777CrossRefPubMedGoogle Scholar
  70. 70.
    Dauby N, Goetghebuer T, Kollmann TR, Levy J, Marchant A (2012) Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis 12:330–340CrossRefPubMedGoogle Scholar
  71. 71.
    Chen JC, Chan CC, Wu CJ, Ou LS, Yu HY, Chang HL, Tseng LY, Kuo ML (2016) Fetal phagocytes take up allergens to initiate T-helper cell type 2 immunity and facilitate allergic airway responses. Am J Respir Crit Care Med 194(8):934–947CrossRefPubMedGoogle Scholar
  72. 72.
    Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD, Holt PG (1998) Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol 160(10):4730–4737PubMedGoogle Scholar
  73. 73.
    Hebel K, Weinert S, Kuropka B, Knolle J, Kosak B, Jorch B, Arens B, Krause E, Braun-Dullaeus RC, Brunner-Weinzierl MC (2014) CD4+ T cells from human neonates and infants are poised spontaneously to run a nonclassical IL-4 program. J Immunol 192:5160–5170Google Scholar
  74. 74.
    Rose S, Lichtenheld M, Foote MR, Adkins B (2007) Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. J Immunol 178:2667–2678CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Webster RB, Rodriguez Y, Klimecki WT, Vercelli D (2007) The human IL-13 locus in neonatal CD4+ T cells is refractory to the acquisition of a repressive chromatin architecture. J Biol Chem 282:700–709CrossRefPubMedGoogle Scholar
  76. 76.
    Szepfalusi Z, Pichler J, Elsasser S, van Duren K, Ebner C, Bernaschek G, Urbanek R (2000) Transplacental priming of the human immune system with environmental allergens can occur early in gestation. J Allergy Clin Immunol 106(3):530–536CrossRefPubMedGoogle Scholar
  77. 77.
    Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG (1999) Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353(9148):196–200CrossRefPubMedGoogle Scholar
  78. 78.
    Hauer AC, Riederer M, Griessl A, Rosegger H, MacDonald TT (2003) Cytokine production by cord blood mononuclear cells stimulated with cows milk proteins in vitro: interleukin-4 and transforming growth factor beta-secreting cells detected in the CD45RO T cell population in children of atopic mothers. Clin Exp Allergy, J British Soc Allergy Clin Immunol 33(5):615–623CrossRefGoogle Scholar
  79. 79.
    Gill TJ 3rd, Repetti CF, Metlay LA, Rabin BS, Taylor FH, Thompson DS, Cortese AL (1983) Transplacental immunization of the human fetus to tetanus by immunization of the mother. J Clin Invest 72(3):987–996CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Rastogi D, Wang C, Mao X, Lendor C, Rothman PB, Miller RL (2007) Antigen-specific immune responses to influenza vaccine in utero. J Clin Invest 117:1637–1646CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Bajetta E, Catena L, Fazio N, Pusceddu S, Biondani P, Blanco G, Ricci S, Aieta M, Pucci F, Valente M, Bianco N, Mauri CM, Spada F (2014) Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study. Cancer 120(16):2457–2463CrossRefPubMedGoogle Scholar
  82. 82.
    Newell EW, Sigal N, Bendall SC, Nolan GP, Davis MM (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36(1):142–152CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA (2015) Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161(5):1202–1214CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J (2014) The placenta harbors a unique microbiome. Sci Transl Med 6:237ra65CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Neonatal Immunity group, Human histopathology and animal modelsInstitut PasteurParisFrance

Personalised recommendations