Triggering of TNFRSF25 promotes CD8+ T-cell responses and anti-tumor immunity

Slebioda, Tomasz J., Rowley, Tania F., Ferdinand, John R., Willoughby, Jane E., Buchan, Sarah L., Taraban, Vadim Y. and Al-Shamkhani, Aymen (2011) Triggering of TNFRSF25 promotes CD8+ T-cell responses and anti-tumor immunity. European Journal of Immunology, 41 (9), 2606-2611. (doi:10.1002/eji.201141477). (PMID:21688261)

Abstract

TNFRSF25 is a member of the TNF receptor superfamily (TNFRSF) that binds to the TNF-like protein TL1A. Although recent studies have demonstrated a role for TNFRSF25 in regulating CD4+ T-cell responses, it remains to be determined if TNFRSF25 functions as a costimulatory receptor for CD8+ T cells. Here, we demonstrate that ectopic expression of TL1A on mouse plasmacytomas promotes elimination of tumor cells in a CD8+ T-cell-dependent manner and renders mice immune to a subsequent challenge with tumor cells. To gain further insight into the role of TNFRSF25 in CD8+ T-cell responses, we analyzed the effect of TNFRSF25 triggering on OT-I TCR transgenic T cells. We demonstrate that TNFRSF25 triggering in vivo with soluble TL1A promotes the proliferation and accumulation of antigen-specific CD8+ T cells as well as their differentiation into CTLs. Furthermore, we show that TNFRSF25 also functions as a costimulatory receptor for memory CD8+ T cells. Thus, TNFRSF25 triggering enhances the secondary expansion of endogenous antigen-specific memory CD8+ T cells. Our data suggest that TNFRSF25 agonists, such as soluble TL1A, could potentially be used to enhance the immunogenicity of vaccines that aim to elicit human anti-tumor CD8+ T cells.

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Contributors

Author: Jane E. Willoughby

Author: Aymen Al-Shamkhani

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