Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon
Young-Jun Ju, Sungwoo Lee, Yoon-Chul Kye, Gil-Woo Lee, Hee-Ok Kim, Cheol‐Heui Yun, Jae-Ho Cho
Abstract
Abstract The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8 + T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5 lo Ly6C – , CD5 hi Ly6C – , and CD5 hi Ly6C + cells. CD5 hi Ly6C + cells differ from CD5 lo Ly6C – and CD5 hi Ly6C – cells in terms of gene expression profiles and functional properties. Moreover, CD5 hi Ly6C + cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5 hi Ly6C + cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8 + T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8 + T cells by co-opting tonic type I interferon signaling.