Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors

The increased susceptibility of neonates to infections has been ascribed to the immaturity of their immune system, More particularly, T cell-dependent responses were shown to be biased rewards a Th2 phenotype, Our studies on the in vitro maturation of umbilical cord blood T cells suggest that the Th2 bias of neonatal response cannot be simply ascribed to intrinsic properties of neonatal T cells. Phenotypically, neonatal CD4(+) T cells are more immature than their adult CD45RO(-)/RA(+) naive counterparts and they contain a subset (10-20%) of CD45RO(-)/RA(+) CD31(-) cells which is very low irt adults and displays some unique functional features, The activation and maturation of neonatal CD4(+) T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12, Activation of adult as well as neonatal CD4(+) T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine i,e, IL-2. In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFN gamma and TNF beta) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells, The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by art autocrine pathway. The ability of IL-12 to prime neonatal CD4(+) T cells for increased production of IL-4 (in addition to IFN gamma) is observed only when CD28 cosignal is minimal. Under optimal activation conditions (i.e. with anti-CD3/B7.1 or allogenic dendritic cells) the response and the maturation, of neonatal and adult naive T cells are similar. Thus the Th2 bias of neonatal immune response cannot be simply ascribed to obvious intrinsic T cell defect but rather to particular conditions of Ag presentation at priming, Unlike CD4(+) T cells, neonatal CD8(+) T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers. Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-I infection in vitro. (C) 1998 Elsevier Science Ltd. All rights reserved.