PMID- 10764820 OWN - NLM STAT- MEDLINE DCOM- 20000816 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 25 DP - 2000 Jun 23 TI - Tumor necrosis factor-alpha production is differently regulated in gamma delta and alpha beta human T lymphocytes. PG - 19282-7 AB - Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the early defense against pathogens. This cytokine is produced by several cell types including T lymphocytes expressing the alphabeta as well as the gammadelta T cell receptor (TcR). In human, the circulating gammadelta T cells, which mostly express Vgamma9Vdelta2 TcR, have been strongly suggested to play an important protective role against infectious agents. These activated cells early produce high amounts of TNF-alpha, which induce a determinant beneficial effect against development of intracellular pathogens; however, sustained production of this cytokine can result in immunopathological diseases. The signals that regulate TNF-alpha production in Vgamma9Vdelta2 T cells are totally unknown. In primary alphabeta T cells, TNF-alpha production was shown to necessitate engagement of the TcR and CD28, and to be independent of the p38 mitogen activated protein kinase pathway. We demonstrate herein that, in contrast to alphabeta T cells, TNF-alpha production in Vgamma9Vdelta2 T lymphocytes is independent of CD28 costimulation and highly dependent on TcR-induced p38 kinase and extracellular signal-regulated kinase 2 pathway activation for optimal cytokine release. Moreover, we bring elements supporting the idea that the "activation threshold" of gammadelta T cells leading to cytokine production is lower than that of alphabeta T cells. FAU - Lafont, V AU - Lafont V AD - INSERM U431, Microbiologie et Pathologie Cellulaire Infectieuse, Universite Montpellier 2, Place Eugene Bataillon, cc 100, 34095 Montpellier cedex 05, France. FAU - Liautard, J AU - Liautard J FAU - Gross, A AU - Gross A FAU - Liautard, J P AU - Liautard JP FAU - Favero, J AU - Favero J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CD28 Antigens) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 0 (Receptors, Antigen, T-Cell, gamma-delta) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - CD28 Antigens/immunology MH - Humans MH - In Vitro Techniques MH - Receptors, Antigen, T-Cell, alpha-beta/*immunology MH - Receptors, Antigen, T-Cell, gamma-delta/*immunology MH - Signal Transduction MH - T-Lymphocytes/immunology/*metabolism MH - Tumor Necrosis Factor-alpha/*biosynthesis EDAT- 2000/04/15 09:00 MHDA- 2000/08/19 11:00 CRDT- 2000/04/15 09:00 PHST- 2000/04/15 09:00 [pubmed] PHST- 2000/08/19 11:00 [medline] PHST- 2000/04/15 09:00 [entrez] AID - S0021-9258(19)80196-5 [pii] AID - 10.1074/jbc.M910487199 [doi] PST - ppublish SO - J Biol Chem. 2000 Jun 23;275(25):19282-7. doi: 10.1074/jbc.M910487199.