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Annual Review of Immunology

Volume 43, 2025

TNF/TNFR Superfamily Members in Costimulation of T Cell Responses—Revisited

Abstract

Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis factor superfamily (TNFSF) members on inflammatory monocyte-derived antigen-presenting cells (APCs) provide a postpriming signal (signal 4) for T cell accumulation, particularly in the tissues. Patients with loss-of-function mutations in TNFR/TNFSF members reveal a critical role for 4-1BB and CD27 in CD8 T cell control of Epstein-Barr virus and other childhood infections and of OX40 in CD4 T cell responses. Here, on the 20th anniversary of a previous article about TNFRSF signaling in T cells, we discuss the effects of endogenous TNFRSF signals in T cells upon recognition of TNFSF members on APCs; the role of TNFRSF members, including TNFR2, on regulatory T cells; and recent advances in the incorporation of TNFRSF signaling in T cells into immunotherapeutic strategies for cancer.

Keyword(s): 4-1BB, CD27, GITR, OX40, T cells, TNFR2
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/content/journals/10.1146/annurev-immunol-082423-040557
2025-04-25
2025-06-19
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/content/journals/10.1146/annurev-immunol-082423-040557
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TNF/TNFR Superfamily Members in Costimulation of T Cell Responses—Revisited
Annual Review of Immunology 43, 113 (2025); https://doi.org/10.1146/annurev-immunol-082423-040557
/content/journals/10.1146/annurev-immunol-082423-040557
/content/journals/10.1146/annurev-immunol-082423-040557
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