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p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells.
J Immunol. 1999 Apr 01; 162(7):3819-29.JI

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.

Authors+Show Affiliations

Autoimmunity/Diabetes Group, John P. Robarts Research Institute, London, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10201899

Citation

Zhang, J, et al. "P38 Mitogen-activated Protein Kinase Mediates Signal Integration of TCR/CD28 Costimulation in Primary Murine T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 7, 1999, pp. 3819-29.
Zhang J, Salojin KV, Gao JX, et al. P38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. J Immunol. 1999;162(7):3819-29.
Zhang, J., Salojin, K. V., Gao, J. X., Cameron, M. J., Bergerot, I., & Delovitch, T. L. (1999). P38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. Journal of Immunology (Baltimore, Md. : 1950), 162(7), 3819-29.
Zhang J, et al. P38 Mitogen-activated Protein Kinase Mediates Signal Integration of TCR/CD28 Costimulation in Primary Murine T Cells. J Immunol. 1999 Apr 1;162(7):3819-29. PubMed PMID: 10201899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. AU - Zhang,J, AU - Salojin,K V, AU - Gao,J X, AU - Cameron,M J, AU - Bergerot,I, AU - Delovitch,T L, PY - 1999/4/14/pubmed PY - 1999/4/14/medline PY - 1999/4/14/entrez SP - 3819 EP - 29 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 162 IS - 7 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10201899/p38_mitogen_activated_protein_kinase_mediates_signal_integration_of_TCR/CD28_costimulation_in_primary_murine_T_cells_ DB - PRIME DP - Unbound Medicine ER -