Neonatal T Cells Produce Significantly Higher Levels of IL-10 Compared to Adult Derived T Cells

Abstract • 122

It is recognised that successful vaccination in neonates has different requirements than in adults although the reasons for this have not been established. The development of effective vaccines is dependent on the generation of effector T cells from naïve T cells. In this study, factors affecting the differentiation of neonatal versus adult CD4+CD45RA+ T cells into T_H1 or T_h2 cells were examined. Highly purified CD4+CD45RA+ T cells from umbilical cord and peripheral blood were stimulated with anti-CD3 in the presence of IL-2. Similar amounts of IFN-γ and IL-4, as measured by ELISA, were produced by adult and cord blood populations. However, IL-10 was produced in cord blood cultures (Mean±SEM; 1822.3±354.8pg/ml, n=6), but was not detectable in adult cultures (n=7). Addition of anti-CD28 further increased IL-10 levels in the cord (Mean±SEM; 2347.2±805.4pg/ml, n=6) but in the adult, IL-10 levels remained below the level of detection in most of the samples tested. Addition of IL-1β almost completely inhibited IL-10 production by neonatal T cells, and repeated stimulation also resulted in reduced IL-10 production. Intracellular cytokine staining demonstrated IL-10 production in neonatal but not in adult cultures. The effects of the T_H1 and T_H2 polarising cytokines, IL-12 and IL-4, on IL-10 production were examined. IL-4 significantly increased IL-10 production in neonatal CD4+CD45RA+ T cell cultures, an effect that was reversed in the presence of neutralising anti-IL-4 antibody. IL-12 promoted IL-10 production in both populations, but only after repeated rounds of stimulation. These results suggest that newborn and adult T cells have similar propensities toward T_H1 and T_H2 type cytokine responses, but that newborn T cells can uniquely express high levels of IL-10 under conditions where adult derived T cells produce none or very low levels. Since IL-10 acts as a major suppression cytokine, this study provides some support for the perceived tolerant or immunosuppressed nature of the newborn immune response and could have important implications for the development of effective vaccine strategies.