Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis.
作者： A P Cope , M Londei , N R Chu , S B Cohen , M J Elliott
DOI: 10.1172/JCI117394
关键词:
摘要: Experiments were designed to test the hypothesis that chronic exposure tumor necrosis factor alpha (TNF) alters function of activated T lymphocytes. Pretreatment tetanus toxoid-specific cell clones with TNF for up 16 d impaired rechallenge proliferative responses antigen in a dose- and time-dependent fashion. IL-2 PHA preserved. Prolonged treatment production IL-2, IL-10, IFN gamma, TNF, lymphotoxin (LT) following stimulation immobilized OKT3, resulted suboptimal expression IL-2R chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared untreated control cells. By contrast, pretreatment cells prolonged periods vitro neutralizing anti-TNF monoclonal antibodies (mAb) enhanced responses, increased lymphokine production, upregulated Tac OKT3. To determine whether exerts immunosuppressive effects on vivo, we studied cell-mediated immunity patients active rheumatoid arthritis (RA), before after chimeric mAb. Treatment restored diminished PBMC mitogens recall antigens towards normal all tested. These data demonstrate persistent vivo impairs immune responses.
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