Differentiation of CD4⁺ T cells into either follicular helper T (T_FH) or type 1 helper T (T_H1) 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 production of the cytokine IL-6 and drove T_FH cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into T_H1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4⁺ T cell differentiation and might instruct vaccine design strategies.

CD4 ⁺ T 细胞分化为滤泡辅助 T (T _FH ) 或 1 型辅助 T (T _H 1) 细胞会影响体液和细胞适应性免疫之间的平衡，但病原体引发不同效应细胞的机制尚不完全清楚。这里我们分析了CD4 ^{+的时空动态}感染重组水泡性口炎病毒 (VSV) 期间的 T 细胞，可诱导早期有效的中和抗体，或重组淋巴细胞脉络丛脑膜炎病毒 (LCMV)，可诱导强烈的细胞反应但中和抗体无效，表达相同的 T 细胞表位。树突状细胞早期暴露于 I 型干扰素 (IFN)，发生在 VSV 感染期间，诱导细胞因子 IL-6 的产生并驱动 T _FH细胞极化，而晚期暴露于 I 型干扰素，发生在 LCMV 感染期间，不诱导 IL-6 并允许分化为 T _H 1 细胞。因此，I 型 IFN 的严格时空调控形成抗病毒 CD4 ⁺T 细胞分化并可能指导疫苗设计策略。