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

• Published in: European journal of immunology 2011-09, Vol.41 (9), p.2606-2611
• Main Authors: Slebioda, Tomasz J, Rowley, Tania F, Ferdinand, John R, Willoughby, Jane E, Buchan, Sarah L, Taraban, Vadim Y, Al-Shamkhani, Aymen
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141477

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 super(+) T-cell responses, it remains to be determined if TNFRSF25 functions as a costimulatory receptor for CD8 super(+) T cells. Here, we demonstrate that ectopic expression of TL1A on mouse plasmacytomas promotes elimination of tumor cells in a CD8 super(+) 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 super(+) 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 super(+) T cells as well as their differentiation into CTLs. Furthermore, we show that TNFRSF25 also functions as a costimulatory receptor for memory CD8 super(+) T cells. Thus, TNFRSF25 triggering enhances the secondary expansion of endogenous antigen-specific memory CD8 super(+) 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 super(+) T cells.