title: CD4+ and CD8+ T cell survival is regulated differentially by protein kinase Ctheta, c-Rel, and protein kinase B.
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.
authors.affiliation: Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Saibil
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.forename: Elissa K
authors.initials: EK
authors.lastname: Deenick
authors.forename: Nicole
authors.initials: N
authors.lastname: Liadis
authors.forename: Alisha R
authors.initials: AR
authors.lastname: Elford
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Vainberg
authors.forename: Heather
authors.initials: H
authors.lastname: Baerg
authors.forename: James R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007527:Isoenzymes / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000276:immunology; D011493:Protein Kinase C / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051020:bcl-X Protein / Q000096:biosynthesis / Q000276:immunology
chemical_list: C494812:Bcl2l1 protein, mouse; D007376:Interleukin-2; D007527:Isoenzymes; D052002:NF-kappa B p50 Subunit; D020569:Proto-Oncogene Proteins c-rel; D051020:bcl-X Protein; D051057:Proto-Oncogene Proteins c-akt; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta