Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon

• DOI: 10.1038/s41467-021-26351-3
• Publication Date: 2021-10-18T19:27:17Z
• Authors: Young-Jun Ju; Sung-Woo Lee; Yoon-Chul Kye; Gil-Woo Lee; Hee-Ok Kim; Cheol-Heui Yun; Jae-Ho Cho
• Keywords: EXPRESSION; 0301 basic medicine; HOMEOSTASIS; 570; SUBSETS; Science; EFFECTOR; 610; Receptor, Interferon alpha-beta; CD8-Positive T-Lymphocytes; Inbred C57BL; CD5 Antigens; Article; Interferon alpha-beta; Mice; 03 medical and health sciences; STRENGTH; Receptors; Animals; Antigens, Ly; Antigens; Cell Proliferation; Receptors, Interferon; Interferon gamma Receptor; Q; Cell Differentiation; CD5; 3. Good health; Mice, Inbred C57BL; MAINTENANCE; Phenotype; STAT1 Transcription Factor; Ly; Interferon Type I; Interferon; REGULATOR; Receptor; Signal Transduction

AbstractThe 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, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+cells. CD5hiLy6C+cells differ from CD5loLy6C–and CD5hiLy6C–cells in terms of gene expression profiles and functional properties. Moreover, CD5hiLy6C+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 CD5hiLy6C+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.