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p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells
Journal article   Peer reviewed

p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells

Jian Zhang, Kostantin V Salojin, Jian-Xin Gao, Mark J Cameron, Isabelle Bergerot and Terry L Delovitch
The Journal of immunology (1950), Vol.162(7), pp.3819-3829
04/01/1999
DOI: 10.4049/jimmunol.162.7.3819
PMID: 10201899

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Abstract

Optimal T cell activation requires two signals, one generated by TCR and another by the CD28 costimulatory receptor. In this study, we investigated the regulation of costimulation-induced mitogen-activated protein kinase (MAPK) activation in primary mouse T cells. In contrast to that reported for human Jurkat T cells, we found that p38 MAPK, but not Jun NH2-terminal kinase (JNK), is weakly activated upon stimulation with either anti-CD3 or anti-CD28 in murine thymocytes and splenic T cells. However, p38 MAPK is activated strongly and synergistically by either CD3/CD28 coligation or PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3/CD28-mediated signaling. Activation of p38 MAPK correlates closely with the stimulation of T cell proliferation. In contrast, PMA-induced JNK activation is inhibited by Ca2+ ionophore. T cell proliferation and production of IL-2, IL-4, and IFN-gamma induced by both CD3 and CD3/CD28 ligation and the nuclear expression of the c-Jun and ATF-2 proteins are each blocked by the p38 MAPK inhibitor SB203580. Our findings demonstrate that p38 MAPK 1) plays an important role in signal integration during costimulation of primary mouse T cells, 2) may be involved in the induction of c-Jun activation and augmentation of AP-1 transcriptional activity, and 3) regulates whether T cells enter a state of functional unresponsiveness.
 T-Lymphocytes - enzymology Humans Proto-Oncogene Proteins c-jun - biosynthesis Proto-Oncogene Proteins c-jun - antagonists & inhibitors Cell Nucleus - enzymology Signal Transduction - immunology Calcium - physiology Cell Nucleus - metabolism T-Lymphocytes - drug effects JNK Mitogen-Activated Protein Kinases Receptors, Antigen, T-Cell - immunology p38 Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Cyclic AMP Response Element-Binding Protein - biosynthesis T-Lymphocytes - secretion Jurkat Cells Mice, Inbred C57BL Cells, Cultured Cytokines - secretion Transcription Factors - antagonists & inhibitors Transcription Factors - biosynthesis CD28 Antigens - immunology Imidazoles - pharmacology CD3 Complex - metabolism Drug Synergism Animals Signal Transduction - drug effects Lymphocyte Activation - drug effects Activating Transcription Factor 2 CD3 Complex - immunology Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors T-Lymphocytes - immunology Mice Mice, Inbred BALB C Pyridines - pharmacology Cytokines - antagonists & inhibitors Enzyme Activation Cell Nucleus - drug effects Calcium-Calmodulin-Dependent Protein Kinases - metabolism

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