Open AccessTumour necrosis factor (TNF) production by T cell receptor‐primed T lymphocytes is a target for low dose methotrexate in rheumatoid arthritis
Author(s) -
Kai Hildner,
Susetta Finotto,
Christoph Becker,
Joerg F. Schlaak,
Peter Schirmacher,
Peter R. Galle,
Elisabeth MärkerHermann,
Markus F. Neurath
Publication year - 1999
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1999.01022.x
Subject(s) - immunology , t cell receptor , priming (agriculture) , t cell , tumor necrosis factor alpha , rheumatoid arthritis , peripheral blood mononuclear cell , methotrexate , cytotoxic t cell , arthritis , medicine , cytokine , biology , immune system , in vitro , biochemistry , botany , germination
Methotrexate (MTX) is an effective immunosuppressive agent in various chronic inflammatory diseases such as rheumatoid arthritis (RA). However, its mechanisms of action are only partially understood. In this study, we assessed the effects of MTX on the differentiation of peripheral blood (PB) CD4 + CD45RA ‘naive’ and CD4 + CD45RO ‘memory’ T cells from healthy controls and patients with RA. Accordingly, purified T cells were primed and restimulated in vitro via the T cell receptor (TCR) in the presence of IL‐2 to generate effector T cells secreting large amounts of Th1 and Th2 cytokines. We observed that low doses of MTX strongly suppress TNF and to a lesser extent interferon‐gamma (IFN‐γ) production by T cells from both healthy donors and RA patients when present during T cell priming via the TCR. Similar data were obtained for TCR‐primed synovial fluid mononuclear cells in RA. In contrast, production of IL‐4 by TCR‐primed CD45RA T cells was significantly increased upon MTX treatment. Interestingly, MTX did not enhance IL‐4 production when present during restimulation of effector CD45RO T cells, although it still suppressed TNF production. The results indicate that MTX effects depend on the stage of T cell activation and identify TNF production by TCR‐primed T lymphocytes as a target for low‐dose MTX treatment in RA. These findings could explain the delayed clinical effects of MTX and may contribute to its potent anti‐inflammatory and immunoregulatory properties.