HMGB2 regulates virus-specific CD8⁺ T cell differentiation and function.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B165
Abstract ID: 4379

Presenting Author:
Jamie-Jean De La Torre , Graduate Student Researcher at Univ. of California, Irvine, Univ. of California, Irvine, Chao Family Comp. Cancer Ctr.

Abstract:

CD8⁺ T cells mediate host defense against acute and chronic Lymphocytic choriomeningitis viral (LCMV) infection. Viral clearance generates functional memory (mem.) CD8⁺ T cells, while chronic infection leads to T cell exhaustion. High mobility group box 2 (HMGB2) protein is a DNA-binding protein that is upregulated in exhausted CD8⁺ T cells and is necessary for maintenance of progenitor exhausted T cells (Tpex). We hypothesize that HMGB2 regulates the early transcriptional programming of virus-specific CD8⁺ T cells during acute and chronic viral infection. To test this, we cotransferred WT and Hmgb2^-/- (KO) LCMV-specific CD8⁺ T cells into WT hosts and tracked their kinetics during acute or chronic LCMV infection. During acute infection, KO T cells were increased by 5dpi and decreased compared to WT by 30dpi. KO cells had increased effector mem. and decreased central mem. and terminal effector mem. phenotypes. Furthermore, we observed reduced cytokine-producing KO mem. T cells compared to WT, indicating reduced functionality. During chronic infection, KO cells expanded more than WT cells by 5dpi but severely decreased as the infection persisted. We detected reduced Tpex and increased T effector exhausted cells within the KO cells by 5dpi. Taken together, these results indicate that HMGB2 plays a key role in the early differentiation process of virus-specific CD8⁺ T cells to influence their programming and function during both acute and chronic infection.