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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i3.10
pages 187-201

The Role of OX40-Mediated Co-stimulation in T-Cell Activation and Survival

William L. Redmond
Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 NE Glisan St., No. 5F37, Portland, OR 97213, USA
Carl E. Ruby
Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 NE Glisan St. 2N35, Portland, OR 97213
Andrew D. Weinberg
Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 NE Glisan St., No. 5F37, Portland, OR 97213, USA

ABSTRACT

The extent of T-cell activation, proliferation, and survival that follows T-cell receptor (TCR) ligation is controlled by several factors, including the strength of TCR stimulation, the availability of prosurvival cytokines, and the presence or absence of co-stimulatory signals. In addition to engagement of the CD28 co-stimulatory receptor by its natural ligands, B7.1 (CD80) and B7.2 (CD86), recent work has begun to elucidate the mechanisms by which signaling through the OX40 (CD134) co-stimulatory receptor, a member of the tumor necrosis factor receptor (TNFR) superfamily, affects T-cell responses. Importantly, OX40 ligation has been shown to augment CD4 and CD8 T-cell clonal expansion, effector differentiation, survival, and in some cases, abrogate the suppressive activity of regulatory FoxP3+CD25+CD4+ T cells. In this review, we focus on the mechanisms regulating OX40 expression on activated T cells as well as the role of OX40-mediated co-stimulation in boosting T-cell clonal expansion, effector differentiation, and survival.