CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IB kinase and NF-B activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-Bdependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-B subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-B sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.

CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 nuclear factor-kappaB subunits on IL-8 and Bcl-xL gene promoters / Marinari, B.; Costanzo, A.; Marzano, V.; Piccolella, Enza; Tuosto, Loretta. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 101:16(2004), pp. 6098-6103. [10.1073/pnas.0308688101]

CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 nuclear factor-kappaB subunits on IL-8 and Bcl-xL gene promoters

MARINARI B.;PICCOLELLA, Enza;TUOSTO, Loretta
2004

Abstract

CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IB kinase and NF-B activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-Bdependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-B subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-B sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/237634
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