The Journal of Experimental Medicine
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Published online 31 March 2003 doi:10.1084/jem.20021610
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© Rockefeller University Press, 0022-1007/2003/4/861 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 861-874

Combined Deficiency of p50 and cRel in CD4+ T Cells Reveals an Essential Requirement for Nuclear Factor {kappa}B in Regulating Mature T Cell Survival and In Vivo Function

Ye Zheng1, Monika Vig2, Jesse Lyons1, Luk Van Parijs2 and Amer A. Beg1

1 Department of Biological Sciences, Columbia University, New York, NY 10027
2 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139

Address correspondence to Amer A. Beg, 1110 Fairchild Center, Department of Biological Sciences, 1212 Amsterdam Avenue, Columbia University, New York, NY 10027. Phone: 212-854-5939; Fax: 212-865-8246; E-mail: aab41{at}columbia.edu

Signaling pathways involved in regulating T cell proliferation and survival are not well understood. Here we have investigated a possible role of the nuclear factor (NF)-{kappa}B pathway in regulating mature T cell function by using CD4+ T cells from p50-/- cRel-/- mice, which exhibit virtually no inducible {kappa}B site binding activity. Studies with these mice indicate an essential role of T cell receptor (TCR)-induced NF-{kappa}B in regulating interleukin (IL)-2 expression, cell cycle entry, and survival of T cells. Our results further indicate that NF-{kappa}B regulates TCR-induced expression of antiapoptotic Bcl-2 family members. Strikingly, retroviral transduction of CD4+ T cells with the NF-{kappa}B–inducing I{kappa}B kinase ß showed that NF-{kappa}B activation is not only necessary but also sufficient for T cell survival. In contrast, our results indicate a lack of involvement of NF-{kappa}B in both IL-2 and Akt-induced survival pathways. In vivo, p50-/- cRel-/- mice showed impaired superantigen-induced T cell responses as well as decreased numbers of effector/memory and regulatory CD4+ T cells. These findings provide the first demonstration of a role for NF-{kappa}B proteins in regulating T cell function in vivo and establish a critically important function of NF-{kappa}B in TCR-induced regulation of survival.

Key Words: T lymphocytes • T cell receptor • cell death • NF-{kappa}B • transcription factor


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