Cytokine receptor signaling in CD4+ T cells (P6305)

Abstract

Infants compared to adults exhibit reduced immune responsiveness and are biased towards a T helper 2 (Th2) response. We hypothesized that this is due to the presence of intrinsic differences in cytokine receptor signaling in CD4+ T cells. We utilized human adult and cord blood (CB) samples to determine whether age-related differences exist in (i) Th1 and Th2 cytokine receptor (R) expression, (ii) STAT phosphorylation, and/or (iii) JAK/STAT signaling. Our data show that a lower percentage of CB compared to adult CD4+ T cells expresses IFNγR1 (P=0.0053). However, absolute numbers of IFNγR1 are higher on CB compared to CD4+ T cells (P=0.0305). In contrast, we did not detect differences in the levels of IL4Rα expression. Consistent with this data, CB CD4+ T cells show lower phosphorylation levels of STAT1, but not STAT6 in response to IFNγ or IL4 stimulation. Furthermore, several genes of the JAK/STAT signaling pathway (e.g. jak1, ifng, stam, isg15 and oas1) were induced at higher magnitude and with faster kinetics in adult compared to CB PBMC after in vitro stimulation with IFNγ. Thus, our data demonstrate that unique age-related differences exist in CD4+ T cell cytokine receptor signaling that may underlie the reduced immune responsiveness and Th2-biased response of infants. Unraveling these molecular mechanisms may aid in pediatric vaccine and therapeutics design.