Abstract
Preterm and small-for-gestational-age (SGA) neonates are vulnerable groups that are susceptible to various microbial infections. Vγ9Vδ2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vγ9Vδ2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vγ9Vδ2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vγ9Vδ2-T cells in the blood. Upon influenza virus stimulation, neonatal Vγ9Vδ2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vγ9Vδ2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion of Vγ9Vδ2-T cells by isopentenyl pyrophosphate (IPP) was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vγ9Vδ2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vγ9Vδ2-T-cell function of neonates may provide a new way to defend against virus infection.
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References
Hallwirth U, Pomberger G, Pollak A, Roth E, Spittler A . Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. Pediatr Allergy Immunol 2004; 15: 513–516.
Rasmussen SA, Hayes EB, Jamieson DJ, O'Leary DR . Emerging infections and pregnancy: assessing the impact on the embryo or fetus. Am J Med Genet A 2007; 143A: 2896–2903.
Liu E, Tu W, Law HK, Lau YL . Decreased yield, phenotypic expression and function of immature monocyte-derived dendritic cells in cord blood. Br J Haematol 2001; 113: 240–246.
Tu W, Cheung PT, Lau YL . Insulin-like growth factor 1 promotes cord blood T cell maturation and inhibits its spontaneous and phytohemagglutinin-induced apoptosis through different mechanisms. J Immunol 2000; 165: 1331–1336.
Chen SF et al. Antiviral CD8 T cells in the control of primary human cytomegalovirus infection in early childhood. J Infect Dis 2004; 189: 1619–1627.
Tu W et al. Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol 2004; 172: 3260–3267.
Born WK, Reardon CL, O'Brien RL . The function of gamma delta T cells in innate immunity. Curr Opin Immunol 2006; 18: 31–38.
Carding SR, Egan PJ . gamma delta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2002; 2: 336–345.
Hu C et al. Antigen-presenting effects of effector memory Vgamma9Vdelta2 T cells in rheumatoid arthritis. Cell Mol Immunol 2012; 9: 245–254.
Zhao H, Xi X, Cui L, He W . CDR3delta-grafted gamma9delta2T cells mediate effective antitumor reactivity. Cellular Mol Immunol 2012; 9: 147–154.
Zhou J, Kang N, Cui L, Ba D, He W . Anti-gammadelta TCR antibody-expanded gammadelta T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies. Cell Mol Immunol 2012; 9: 34–44.
Qin G et al. Phenotypic and functional characterization of human gammadelta T-cell subsets in response to influenza A viruses. J. Infect Dis 2012; 205: 1646–1653.
Qin G et al. Type 1 responses of human Vgamma9Vdelta2 T cells to influenza A viruses. J Virol 2011; 85: 10109–10116.
Tu W et al. The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a gammadelta T cell population in humanized mice. J Exp Med 2011; 208: 1511–1522.
Qin G et al. Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses. J Infect Dis 2009; 200: 858–865.
Zheng J et al. Generation of human Th1-like regulatory CD4+ T cells by an intrinsic IFN-gamma- and T-bet-dependent pathway. Eur J Immunol 2011; 41: 128–139.
Musha N et al. Expansion of CD56+ NK T and gamma delta T cells from cord blood of human neonates. Clin Exp Immunol 1988; 113: 220–228.
Okah FA, Cai JW, Dew PC, Hoff GL . Risk Factors for Recurrent Small-for-Gestational-Age Birth. Am J Perinat 2010; 27: 1–7.
Lehmann I et al. T cell reactivity in neonates from an East and a West German city—results of the LISA study. Allergy 2002; 57: 129–136.
Alberto EJC, Shimojo N, Aoyagi M, Kohno Y . Differential effects of tumour necrosis factor-alpha and interleukin-12 on isopentenyl pyrophosphate-stimulated interferon-gamma production by cord blood V gamma 9 T cells. Immunology 2009; 127: 171–177.
Drohan L et al. Selective developmental defects of cord blood antigen-presenting cell subsets. Hum Immunol 2004; 65: 1356–1369.
Lappalainen M, Roponen M, Pekkanen J, Huttunen K, Hirvonen MR . Maturation of cytokine-producing capacity from birth to 1 yr of age. Pediatr Allergy Immunol 2009; 20: 714–725.
Tissieres P et al. Innate immune deficiency of extremely premature neonates can be reversed by interferon-gamma. Plos One 2012; 7: e32863.
Marodi L . Innate cellular immune responses in newborns. Clin Immunol 2006; 118: 137–144.
Filias A et al. Phagocytic ability of neutrophils and monocytes in neonates. BMC Pediatr 2011; 11: 29.
Perez A, Bellon JM, Gurbindo MD, Munoz-Fernandez MA . Impairment of stimulation ability of very-preterm neonatal monocytes in response to lipopolysaccharide. Hum Immunol 2010; 71: 151–157.
Hurtado CW et al. Innate immune function in placenta and cord blood of hepatitis C-seropositive mother-infant dyads. Plos One 2010; 5: e12232.
Azizia M, Lloyd J, Allen M, Klein N, Peebles D . Immune status in very preterm neonates. Pediatrics 2012; 129: E967–E974.
Beloosesky R et al. Maternal lipopolysaccharide-induced inflammation during pregnancy programs impaired offspring innate immune responses. Am J Obstet Gynecol 2010; 203: 185.e1–4.
Bukowski JF, Morita CT, Brenner MB . Recognition and destruction of virus-infected cells by human gamma delta CTL. J Immunol 1994; 153: 5133–5140.
Halary F et al. Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells. J Exp Med 2005; 201: 1567–1578.
Poccia F et al. Anti-severe acute respiratory syndrome coronavirus immune responses: the role played by V gamma 9V delta 2 T cells. J Infect Dis 2006; 193: 1244–1249.
Sciammas R, Bluestone JA . TCR gamma delta cells and viruses. Microbes Infect 1999; 1: 203–212.
Poccia F et al. Antiviral reactivities of gammadelta T cells. Microbes Infect 2005; 7: 518–528.
Poccia F et al. Vgamma9Vdelta2 T cell-mediated non-cytolytic antiviral mechanisms and their potential for cell-based therapy. Immunol Lett 2005; 100: 14–20.
Poccia F et al. CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes. J Immunol 1997; 159: 6009–6017.
Campos Alberto EJ, Shimojo N, Aoyagi M, Kohno Y . Differential effects of tumour necrosis factor-alpha and interleukin-12 on isopentenyl pyrophosphate-stimulated interferon-gamma production by cord blood Vgamma9 T cells. Immunology 2009; 127: 171–177.
Strunk T, Currie A, Richmond P, Simmer K, Burgner D . Innate immunity in human newborn infants: prematurity means more than immaturity. J Matern Fetal Neonatal Med 2011; 24: 25–31.
Giannoni E et al. Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns. Infect Immunol 2011; 79: 2690–2698.
Beetz S et al. Innate immune functions of human gammadelta T cells. Immunobiology 2008; 213: 173–182.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 30973235 and 81170606), the Science and Technology project of the Sichuan Science and Technology Department (2010SZ0110), the General Research Fund from the Research Grants Council of Hong Kong (HKU 781211M) and the Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR, China (AoE/M-12/06).
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Li, J., Li, H., Mao, H. et al. Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates. Cell Mol Immunol 10, 253–260 (2013). https://doi.org/10.1038/cmi.2012.78
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DOI: https://doi.org/10.1038/cmi.2012.78
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