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 language | English |
|---|---|
| Pages (from-to) | 7135-7139 |
| Number of pages | 5 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 12 |
| Publication status | Published - Dec 15 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=10344259631&partnerID=8YFLogxK
M3 - Article
VL - 173
SP - 7135
EP - 7139
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -