The role of OX40-mediated co-stimulation in T-cell activation and survival.
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.
Redmond
William L
WL
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.
Ruby
Carl E
CE
Weinberg
Andrew D
AD
D000818:Animals; D015703:Antigens, CD; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D053262:Receptors, OX40 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053278:OX40 Ligand; D011948:Receptors, Antigen, T-Cell; D053262:Receptors, OX40