The TGF-β -- Eomes axis maintains stemness in TCF-1+ CD8+ T cells by restricting tissue egress from secondary lymphoid tissues.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B739
Abstract ID: 5451

Presenting Author:
John Im , Graduate Student at UT Hlth. San Antonio

Abstract:

T-cell exhaustion is characterized by dysfunctional cytotoxic T lymphocytes (CTLs) that express inhibitory and exhaustion markers, such as programmed cell death 1 (PD-1) and CD101, with a reduced capacity to clear antigens. Exhausted CTLs arise from ‘stem-like’ precursors that express T cell factor-1 (TCF-1) and have a unique gene signature similar to hematopoietic stem cells. These self-renewing precursors reside in secondary lymphoid tissues, requiring Transforming growth factor beta (TGF-β) to maintain their residency and mitigate their effector differentiation, partially via controlling the expression of a4 integrins. Downstream of TGF-β, expression of the transcription factor Eomes has been associated with greater levels of exhaustion and is highly upregulated in terminally exhausted cells. Using a chronic lymphocytic choriomeningitis virus (LCMV) infection model in wild-type B6 mice, we found that TGF-β inhibited Eomes expression in TCF-1+ stem-like CD8 T cells. And that deletion of Eomes largely corrected the defects in TCF-1+ stem-like T cells lacking TGF-β receptor signaling. Our data indicate that the TGF-β -- Eomes axis helps to maintain stem-like TCF1+ precursor cells within lymphoid tissues, and that this pathway could be targeted to reinvigorate exhausted CD8+ T cells.