Cd4+ and Cd8+ T Cell Survival is Regulated Differentially by Protein Kinase Ctheta, C-rel, and Protein Kinase B.
From: Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Mar 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 5
- Pages: 2932-9
- Medium: Print
- Language: English
- Citation (JAMA): Saibil Samuel D, Jones Russell G, Deenick Elissa K, et al. Cd4+ and Cd8+ T Cell Survival is Regulated Differentially by Protein Kinase Ctheta, C-rel, and Protein Kinase B.. J. Immunol. Mar 2007;178:2932-9
Abstract
An effective immune response requires the expansion and survival of a large number of activated T cells. This study compared the role of protein kinase C (PKC)theta and associated signaling molecules in the survival of activated primary CD4+ vs CD8+ murine T cells. We demonstrate that the absence of PKCtheta resulted in a moderate survival defect in CD4+ T cells and a striking survival defect of CD8+ T lymphocytes. CD8+ T cells lacking the c-Rel, but not the NF-kappaB1/p50, member of the NF-kappaB family of transcription factors displayed a similar impairment in cell survival as PKCtheta(-/-) CD8(+) T lymphocytes. This implicates c-Rel as a key target of PKCtheta-mediated survival signals in CD8+ T cells. In addition, both c-Rel(-/-) and PKCtheta(-/-) T cells also displayed impaired expression of the antiapoptotic Bcl-x(L) protein upon activation. Changes in Bcl-x(L) expression, however, did not correlate with the survival of CD4+ or CD8+ lymphocytes. The addition of protein kinase B-mediated survival signals could restore partially CD4+ T cell viability, but did not dramatically influence CD8+ survival. Active protein kinase B was also unable to restore proliferative responses in CD8+ PKCtheta(-/-) T cells. The survival of CD4+ and CD8+ T cells deficient in either PKCtheta or c-Rel, however, was promoted by the addition of IL-2. Collectively, these data demonstrate that CD4+ and CD8+ T cell survival signals are differentially programmed.
Mesh Headings (Keywords): Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Survival, Gene Expression Regulation, Interleukin-2, Isoenzymes, Lymphocyte Activation, Mice, Mice, Knockout, NF-kappa B p50 Subunit, Protein Kinase C, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-rel, Signal Transduction, bcl-X Protein
Check for Full Text / PubMed Unique Identifier (PMID): 17312138
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