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TCF-1 in CD8 T cells separates GVHD from GVL

Harris, R.; Mammadli, M.; May, A.; Yang, Q.; Fung, I. T. H.; Sen, J. M.; Karimi, M.

2021-03-23 immunology
10.1101/2021.03.22.436494 bioRxiv
Show abstract

T Cell Factor-1, encoded by TCF-7, is a transcription factor that plays an essential role during T cell development and differentiation. In this manuscript we utilized a pre-clinical model provided evidence that TCF-7 is dispensable for the anti-tumor response, and that TCF-7 suppresses key transcriptional factors Eomes and T-bet and molecules responsible for peripheral CD8 T cell cytolytic function. We discovered that TCF-7 regulates NKG2D expression on naive and activated mouse CD8 T cells, and that peripheral CD8 T cells from TCF-7 cKO utilize NKG2D to clear tumor cells. We also provide evidence that TCF-7 regulates key signaling molecules, including LCK, LAT, ITK, PLC-{gamma}1, P65, ERKI/II, and JAK/STATs required for peripheral CD8 T cell persistent function. Our data transcriptomic and protein data uncovered the mechanism of how TCF-7 impacting peripheral CD8 T cell inflammatory cytokine production, CD8 T cell activation, and apoptosis. Our pre-clinical model showed that CD8 T cells from TCF-7 cKO mice did not cause GVHD, but effectively cleared primary tumor cells.

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