title: Activation of p38 mitogen-activated protein kinase is critical step for acquisition of effector function in cytokine-activated T cells, but acts as a negative regulator in T cells activated through the T-cell receptor.
abstract: Peripheral blood CD4(+) CD45RO(+) T cells activated in vitro are able to induce expression of tumour necrosis factor-α (TNF-α) in monocytes via a contact-dependent mechanism. Activation is achieved either with interleukin-2 (IL-2)/IL-6/TNF-α over an 8-day period or cross-linking CD3 using anti-CD3 antibody for 48 hr. In this paper, we show that the p38 mitogen-activated protein kinase (MAPK) signalling pathway played different roles in the generation of effector function in these two types of activated T cells. In anti-CD3 activated T cells, p38 MAPK is a negative regulator for anti-CD3 induced cell proliferation and has no significant effect on the acquisition of either the effector function (induction of monocyte-derived TNF-α) or production of T-cell cytokines. In contrast, the p38 MAPK signalling pathway is required for the acquisition of cytokine-induced effector function and promotes cell proliferation and cytokine production.
authors.affiliation: Kennedy Institute of Rheumatology Division, Imperial College London, London, UK.
authors.forename: Ching
authors.initials: C
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Beavis
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Palfreeman
authors.forename: Parisa
authors.initials: P
authors.lastname: Amjadi
authors.forename: Alan
authors.initials: A
authors.lastname: Kennedy
authors.forename: Fionula M
authors.initials: FM
authors.lastname: Brennan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004789:Enzyme Activation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D048051:p38 Mitogen-Activated Protein Kinases; D017493:Leukocyte Common Antigens