Citations 1
Cutting Edge: Cbl-b: One of the Key Molecules Tuning CD28- and CTLA-4-Mediated T Cell Costimulation
Gál, István, Vermes, Csaba , Alegre, Maria-Luisa, Shao, Qing , Adarichev, Vyacheslava, Xu, Xuemei , Koreny, Tamás, Mikecz, Katalin , Finnegan, Alison, Glant, Tibor T., Zhang, Jian , Li, Dongdong , Alegre, Maria‐Luisa , Chong, Anita S. , Chen, Lieping , Adarichev, Vyacheslav A.
The Journal of Immunology | April 20, 2014 | Volume: 173 | Issue: 12 | Pages: 7135-7139
Abstract Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support of this finding, Cbl-b expression in CTLA-4 knockout (KO) T cells is significantly reduced, and treating CTLA-4KO mice with human CTLA-4Ig to block CD28-B7 interaction restores Cbl-b expression on T cells. Furthermore, CD28 and CTLA-4 costimulatory effects are compromised in Cbl-bKO T cells. These observations indicate that CD28 and CTLA-4 tightly regulate Cbl-b expression which is critical for establishing the threshold for T cell activation.