Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8⁺ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.

对细胞内病原体的有效反应的特点是 T 细胞克隆对其同源肽具有广泛的亲和力范围和多样化的功能表型。如何在整个反应过程中选择 T 细胞克隆以保留广泛的亲和力仍不清楚。在这里，我们证明了 CD8 ⁺ T 细胞对细胞因子 IFN-γ 的直接感应协调了感染过程中的亲合力和分化。 IFN-γ促进低亲和力T细胞的扩增，使其克服高亲和力T细胞的选择性优势，同时增强高亲和力T细胞进入记忆池，从而降低初级反应和免疫反应的平均亲和力。增加记忆反应。在这种情况下，IFN-γ主要由虚拟记忆T细胞提供，虚拟记忆T细胞是一种具有记忆特征的未经历过抗原的子集。总的来说，我们认为 IFN-γ 和虚拟记忆 T 细胞通过协调 T 细胞的亲和力和命运来发挥关键的免疫调节作用。