TGF-β enhances TCF-1+ expression CD8 T cells within secondary lymphoid tissues partly through Eomesodermin nuclear localization 3440

Abstract Description Cytotoxic T lymphocytes (CTLs) that are constantly stimulated with antigen, such as during chronic infection or disease, over express multiple inhibitory receptors (e.g. PD-1, LAG-3, etc.) and accumulate epigenetic changes, becoming dysfunctional and eventually entering an irreversible state of terminal exhaustion. Stem-like precursors to exhaustion, T cell factor-1 (TCF-1)+ CD8 T cells have a transcriptional profile similar to hematopoietic stem cells and self-renew within secondary lymphoid tissues (e.g. Spleen and Lymph nodes). Mature, activated CTLs utilize Transforming growth factor beta (TGF-β) signaling to mitigate their effector clonal expansion partly through a4 integrin expression. Utilizing a chronic lymphocytic choriomeningitis virus (LCMV) infection model, we co-transferred mixed antigen specific wildtype and TGF-β knockout CD8+ T cells (P14) into LCMV infected host mice. Our data revealed that removing TGF-β signaling inhibited Eomesodermin (Eomes) gene expression in TCF-1+ CTLs, and this was correlated with lower Eomes nuclear localization compared to its antagonistic T-box transcription factor T-bet. Our data suggest that TGF-β helps to retain stem-like TCF-1+ CD8 T cells within secondary lymphoid tissues, partly through Eomes signaling. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)