Abstract CD4 ^+ T cells play a critical role in antiviral humoral and cellular immune responses. We have previously reported that subcutaneous lymphocytic choriomeningitis virus (s. c. LCMV) infection is characterized by a stark compartmentalization of CD4 ^+ T cells, leading to strong T ₇ 1 cell polarization but virtually absent T follicular helper (T ₅₇) cells, key drivers of humoral immunity. Here, we investigate the mechanisms responsible for this impaired T ₅₇ differentiation. We show that T-bet ^+ cells induced by LCMV infection encompass a T ₇ 1 cell subset expressing granzyme B (GzmB), and a Tcf-1 ^+ cell subset that retains the potential for T ₅₇ differentiation without expressing mature T ₅₇ markers. Notably, IFN-γ blockade enables full differentiation of Tcf-1 ^+ cells into T ₅₇ cells, formation of germinal centers, and increased antibody production. Suppression of T ₅₇ cells by IFN-γ is not directly mediated by CD4 ^+ T cells but rather involves another cell type, likely dendritic cells (DCs). Our study provides novel insights into the mechanisms underlying early CD4 ^+ T-cell polarization and humoral responses to viruses, with the potential to facilitate the development of effective vaccine strategies.
Sala et al. (Tue,) studied this question.