Induction of CD4 T cell proliferation andin vitroTh1-like cytokine responses to measles virus

Abstract

Mechanisms that lead to induction of life-long immunity to measles virus (MV) are poorly understood. In the present study, we have assessed the activation, proliferation and cytokine secreting function of peripheral blood T cells from MV immune individuals. Expression of cell blastogenesis markers, such as increased forward light scatter and CD38 expression, peaked 5-7 days after infection of peripheral blood mononuclear cells (PBMC) with the live attenuated Edmonston strain of MV. Subset analysis revealed that both CD3- and CD3+ cells expressed activation markers but that the CD3+ T cells predominated late in the culture period corresponding to maximal proliferation and cell recovery. The majority of CD3+ T cells consisted of CD4+CD8- cells. IFN-gamma and IL-4 production similarly showed optimal production late in culture. Depletion of CD4 cells prior to culture and MV stimulation completely abrogated both IFN-gamma and IL-4 production, whereas depletion of CD8 cells did not diminish production, suggesting that CD4+CD8- T cells were principally involved in production of these cytokines. Finally, optimal IFN-gamma production was elicited at high MV doses and IL-4 at much lower doses. These results suggest that among MV immune individuals, in vitro responses to measles are dominated by CD4+ T cells that, depending on antigen dose, primarily produce a Th1-like and, to a lesser extent, a Th1/Th2-mixed pattern of cytokine release.