Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation

Dongdong Li, István Gál, Csaba Vermes, Maria Luisa Alegre, Anita S.F. Chong, Lieping Chen, Qing Shao, Vyacheslava Adarichev, Xuemei Xu, Tamas Koreny, Katalin Mikecz, Alison Finnegan, Tibor T. Glant, Jian Zhang

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7135-7139
Number of pages5
JournalJournal of Immunology
Volume173
Issue number12
DOIs
Publication statusPublished - Dec 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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