TY - JOUR
T1 - Cutting edge
T2 - Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation
AU - Li, Dongdong
AU - Gál, István
AU - Vermes, Csaba
AU - Alegre, Maria Luisa
AU - Chong, Anita S.F.
AU - Chen, Lieping
AU - Shao, Qing
AU - Adarichev, Vyacheslava
AU - Xu, Xuemei
AU - Koreny, Tamas
AU - Mikecz, Katalin
AU - Finnegan, Alison
AU - Glant, Tibor T.
AU - Zhang, Jian
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/12/15
Y1 - 2004/12/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.173.12.7135
DO - 10.4049/jimmunol.173.12.7135
M3 - Article
C2 - 15585834
AN - SCOPUS:10344259631
VL - 173
SP - 7135
EP - 7139
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -