Monocyte - Mediated Regulation of Antigen - Driven IFNgamma Production by T Cells. The Role of Endogenously Produced TNF

Abstract

The question was asked whether tumour necrosis factor alpha (TNF) is involved in regulation of interferon gamma (IFNgamma) 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 IFNgamma was assessed after 3 days of culture. Preincubation of monocytes with rTNF enhanced their ability to induce IFNgamma production while TNF synthesis inhibitors decreased it. Anti-TNF and anti-TNF-R2 monoclonal antibodies (mAbs) inhibited monocyte ability to present PPD for IFNgamma 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.