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

Young-Jun Ju, Sung-Woo Lee, Yoon-Chul Kye, Gil-Woo Lee, Hee-Ok Kim, Cheol-Heui Yun () and Jae-Ho Cho ()
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Young-Jun Ju: Seoul National University
Sung-Woo Lee: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology
Yoon-Chul Kye: Seoul National University
Gil-Woo Lee: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology
Hee-Ok Kim: Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun Hospital
Cheol-Heui Yun: Seoul National University
Jae-Ho Cho: Chonnam National University Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-15

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, 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.

Date: 2021
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DOI: 10.1038/s41467-021-26351-3

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