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 journalArticle

75 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
Publication statusPublished - Dec 15 2004
Externally publishedYes

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T-Lymphocytes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Li, D., Gál, I., Vermes, C., Alegre, M. L., Chong, A. S. F., Chen, L., ... Zhang, J. (2004). Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. Journal of Immunology, 173(12), 7135-7139.

Cutting edge : Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. / Li, Dongdong; Gál, István; Vermes, Csaba; Alegre, Maria Luisa; Chong, Anita S F; Chen, Lieping; Shao, Qing; Adarichev, Vyacheslava; Xu, Xuemei; Koreny, Tamas; Mikecz, Katalin; Finnegan, Alison; Glant, Tibor T.; Zhang, Jian.

In: Journal of Immunology, Vol. 173, No. 12, 15.12.2004, p. 7135-7139.

Research output: Contribution to journalArticle

Li, D, Gál, I, Vermes, C, Alegre, ML, Chong, ASF, Chen, L, Shao, Q, Adarichev, V, Xu, X, Koreny, T, Mikecz, K, Finnegan, A, Glant, TT & Zhang, J 2004, 'Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation', Journal of Immunology, vol. 173, no. 12, pp. 7135-7139.
Li D, Gál I, Vermes C, Alegre ML, Chong ASF, Chen L et al. Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. Journal of Immunology. 2004 Dec 15;173(12):7135-7139.
Li, Dongdong ; Gál, István ; Vermes, Csaba ; Alegre, Maria Luisa ; Chong, Anita S F ; Chen, Lieping ; Shao, Qing ; Adarichev, Vyacheslava ; Xu, Xuemei ; Koreny, Tamas ; Mikecz, Katalin ; Finnegan, Alison ; Glant, Tibor T. ; Zhang, Jian. / Cutting edge : Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. In: Journal of Immunology. 2004 ; Vol. 173, No. 12. pp. 7135-7139.
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