ausblenden:
Schlagwörter:
Animals; Antigens, CD28/immunology; Cell Division; Genes, Reporter; Humans; Interleukin-2/genetics/secretion; Ionomycin/pharmacology; Ionophores/pharmacology; Isoenzymes/genetics/physiology; Jurkat Cells; Luciferases/biosynthesis/genetics; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Muromonab-CD3/pharmacology; Phorbol 12,13-Dibutyrate/pharmacology; Promoter Regions (Genetics)/genetics; Protein Kinase C/deficiency/genetics/*physiology; Receptors, Antigen, T-Cell/physiology; Recombinant Fusion Proteins/physiology; Research Support, Non-U.S. Gov't; Signal Transduction; T-Lymphocytes/enzymology/immunology; Transfection
Zusammenfassung:
PKCbeta has been established to be essential in B cell receptor (BCR) signaling. Additionally, a critical role of PKCbeta in TCR/CD28-stimulated regulation of IL-2 gene transcription but also exocytotic IL-2 secretion was observed in leukemic T cell lines. To now study the physiological function of PKCbeta in primary CD3(+) T cells, we used our established PKCbeta null mice. Unexpectantly, we did not reveal any defect in the development and function of T cells. Proliferative responses as well as IL-2 cytokine secretion of PKCbeta-deficient CD3(+) T cells induced by allogenic MHC, plate-bound anti-CD3 antibodies (with or without anti-CD28 costimulation), or mitogenic stimuli such as phorbol ester and Ca(2+) ionophore were comparable with wild-type controls. Thus, PKCbeta-deficient T cells had similar physiological thresholds for activation in vitro. These findings suggest that PKCbeta plays a redundant role in TCR-induced regulation of IL-2 cytokine production and T cell proliferation.
