Format

Send to

Choose Destination
J Immunol. 2004 Dec 15;173(12):7135-9.

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

Author information

1
Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.

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.

PMID:
15585834
DOI:
10.4049/jimmunol.173.12.7135
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center