Monocyte-mediated regulation of antigen-driven IFN gamma production by T cells. The role of endogenously produced TNF.
The question was asked whether tumour necrosis factor alpha (TNF) is involved in regulation of interferon gamma (IFN gamma) production by T cells. Monocytes were exposed to exogenous TNF or to TNF synthesis inhibitors (pentoxifylline, PTX and adriamycin, ADR) and then used as antigen (PPD) presenting cells for autologous T cells. The ability of T lymphocytes to release IFN gamma was assessed after 3 days of culture. Preincubation of monocytes with rTNF enhanced their ability to induce IFN gamma production while TNF synthesis inhibitors decreased it. Anti-TNF and anti-TNF-R2 monoclonal antibodies (mAbs) inhibited monocyte ability to present PPD for IFN gamma production which suggested that endogenously produced TNF by monocytes had to be released and acted on TNF-R2 on the monocyte surface. The enhancing effect of exogenous TNF was also abrogated by anti-TNF-R2 mAb. Pretreatment of monocytes with rTNF enhanced, while pretreatment with PTX decreased, PPD-induced IL-6 production. An increased production of IL-4 was found in cultures of PTX-treated, PPD-pulsed monocytes with T cells. This may indicate that in the relative absence of monocyte costimulatory signal(s), probably IL-6, Th2 cells are stimulated. These results indicate that TNF is involved in control of monocyte-mediated regulation of cytokine production by T cells.
Mytar
B
B
Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Cracow, Poland.
Wołoszyn
M
M
Ruggiero
I
I
Pryjma
J
J
Zembala
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010431:Pentoxifylline / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014373:Tuberculin / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D004317:Doxorubicin; D007371:Interferon-gamma; D010431:Pentoxifylline