HMGB2 regulates the differentiation and stemness of exhausted CD8⁺ T cells during chronic viral infection and cancer.

ABSTRACT: Chronic infections and cancers evade the host immune system through mechanisms that induce T cell exhaustion. The heterogeneity within the exhausted CD8⁺ T cell pool has revealed the importance of stem-like progenitor (Tpex) and terminal (Tex) exhausted T cells, although the mechanisms underlying their development are not fully known. Here we report High Mobility Group Box 2 (HMGB2) protein expression is upregulated and sustained in exhausted CD8⁺ T cells, and HMGB2 expression is critical for their differentiation. Through epigenetic and transcriptional programming, we identify HMGB2 as a cell-intrinsic regulator of the differentiation and maintenance of Tpex cells during chronic viral infection and in tumors. Despite Hmgb2^-/- CD8⁺ T cells expres

SUBMITTER: Neubert EN 

PROVIDER: S-EPMC10499904 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature