Immune mechanisms associated with altered infant CD4+ T cell function (57.20)

Abstract

Infant, when compared to adult, CD4+ T cell responses are characterized by a T helper 2 bias and reduced IFN-γ production. We hypothesized that the (1) expression of genes important in TCR signaling is age-dependent and (2) transcription factors involved in cytokine signaling (e.g. signal transducer and activator of transcription (STATs), are differentially activated in infant and adult CD4+ T cells. Naïve and differentiated CD4+ T cells from 2 to 6 months old infant rhesus macaques were FACS-purified, stimulated with anti-CD3 and anti-CD28 antibodies, and analyzed by a Rhesus Th1/2/3 PCR array. The results showed an age-dependent increase in genes associated with Th1 development (e.g. T-bet). Next, human and/or rhesus cord and adult blood samples were stimulated with IL-2, IFN-γ or IL-4 and analyzed by Phosflow for the phosphorylation of STAT5, 1, or 6, respectively. While both infant and adult CD4+ T cells expressed a high percentage of phosphorylated STAT6 positive cells, adult CD4+ T cells had significantly higher frequencies of phosphorylated STAT5 and STAT1 positive CD4+ T cells. Thus, our data indicate that mechanisms of T cell activation differ between infant and adult CD4+ T cells. Defining these differences in distinct signaling pathways may provide novel and critical insights into pediatric HIV vaccine and therapeutics design.