Effect of interleukin-7 and -15 on activation of purified umbilical cord blood and adult peripheral blood CD4+ T cells

Abstract

We investigated the effect of two IL-2 receptor gamma chain (IL-2R-gammac)-signaling cytokines, IL-7 and IL-15, on the activation of purified CD4+ lymphocytes from umbilical cord blood (CB) and adult peripheral blood (APB) by assessing the expression of the IL-2 receptor-alpha (CD25) and Fas (CD95) on CD45RA+ (naïve) and CD45RO+ (memory) CD4+ subsets. Induced CD40L (CD154) expression following phorbol 12-myristate 13-acetate and ionomycin (P+I) stimulation was also examined on cultured CB CD4+ cells. Incubation with IL-15 at 10 ng/ml resulted in a significant increase in the mean fluorescence intensity (MFI) of CD25 on CB CD4+/CD45RA+ cells (exceeding those of APB) without affecting the percentage of CD25-expressing CD45RA+ cells (%CD25/CD45RA). In contrast, both CD25 MFI and %CD25/CD45RA were enhanced on IL-15-treated APB CD4+ cells. CD95 expression (both percent expression and MFI) on CB CD4+/CD45RA+ cells were also enhanced by IL-15, but to a lesser extent compared to the response of ABP. IL-7, used at a concentration equivalent to IL-15, had little effect on APB CD25/CD95 and CB CD25 expression, but did enhance %CD95 expression on CB CD4+/CD45RA+ cells. Both IL-7 and IL-15 could augment the P+I-induced CD40L expression on CB CD4+/CD45RA+ T cells. However, the enhancing effect of IL-15 on CB CD40L/CD45RA expression was more sustained than that of IL-7. Thus, our study demonstrated differential activation of CB CD4+/CD45RA+ cells in response to IL-7 and IL-15 compared to adult counterparts, and the different T-enhancing function between IL-15 and IL-7.