Spatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4(+) T cells

Differentiation of CD4(+) T cells into either follicular helper T (T(FH)) or type 1 helper T (T(H)1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here, we analyzed the spatiotemporal dynamics of CD4(+) T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response, but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced the production of the cytokine IL-6 and drove T(FH) cell polarization, while late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into T(H)1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4(+) T cell differentiation, and might instruct vaccine design strategies.