CD28 Delivers a Unique Signal Leading to the Selective Recruitment of RelA and P52 NF-kappaB Subunits on IL-8 and Bcl-xL Gene Promoters

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Apr 14

PMID 15079071

Citations 36

Authors

Barbara Marinari

Antonio Costanzo

Valeria Marzano

Enza Piccolella

Loretta Tuosto

Affiliations

Soon will be listed here.

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 IkappaB kinase and NF-kappaB 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-kappaB-dependent 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-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB 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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