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

doi:10.4049/jimmunol.173.12.7135

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

Journal article

Peer reviewed

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, …

The Journal of immunology (1950), Vol.173(12), pp.7135-7139

12/15/2004

DOI: 10.4049/jimmunol.173.12.7135

PMID: 15585834

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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.

T-Lymphocyte Subsets - immunology

Adjuvants, Immunologic - pharmacology

Cell Proliferation

T-Lymphocyte Subsets - cytology

Humans

Ubiquitin-Protein Ligases - physiology

Immunoconjugates - pharmacology

Lymphocyte Activation - genetics

Lymphocyte Activation - immunology

Abatacept

CD28 Antigens - genetics

Proto-Oncogene Proteins c-cbl

Female

B7-1 Antigen - pharmacology

Growth Inhibitors - pharmacology

CD28 Antigens - physiology

Mice, Inbred C57BL

Cells, Cultured

B7-1 Antigen - metabolism

Ubiquitin-Protein Ligases - biosynthesis

Antigens, Differentiation - physiology

Mice, Knockout

CTLA-4 Antigen

Drug Synergism

Adaptor Proteins, Signal Transducing - physiology

Animals

T-Lymphocyte Subsets - metabolism

Adaptor Proteins, Signal Transducing - deficiency

Adaptor Proteins, Signal Transducing - genetics

Ubiquitin-Protein Ligases - deficiency

Adaptor Proteins, Signal Transducing - biosynthesis

Antigens, Differentiation - genetics

Mice

Mice, Inbred BALB C

Ubiquitin-Protein Ligases - genetics

Antigens, CD

Details

Title: Subtitle: Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation
Creators: Dongdong Li - Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA
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
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.173(12), pp.7135-7139
DOI: 10.4049/jimmunol.173.12.7135
PMID: 15585834
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AR049047 / NIAMS NIH HHS AR047412 / NIAMS NIH HHS AR049775 / NIAMS NIH HHS
Language: English
Date published: 12/15/2004
Academic Unit: Pathology
Record Identifier: 9984047710302771

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