MONOCYTE-MEDIATED REGULATION OF ANTIGEN-DRIVEN IFNGAMMA PRODUCTION BYT-CELLS - THE ROLE OF ENDOGENOUSLY PRODUCED TNF

The question was asked whether tumour necrosis factor alpha (TNF) is i nvolved in regulation of interferon gamma (IFNgamma) production by T c ells. Monocytes were exposed to exogenous TNF or to TNF synthesis inhi bitors (pentoxifylline, PTX and adriamycin, ADR) and then used as anti gen (PPD) presenting cells for autologous T cells. The ability of T ly mphocytes to release IFNgamma was assessed after 3 days of culture. Pr eincubation of monocytes with rTNF enhanced their ability to induce IF Ngamma production while TNF synthesis inhibitors decreased it. Anti-TN F and anti-TNF-R2 monoclonal antibodies (mAbs) inhibited monocyte abil ity to present PPD for IFNgamma production which suggested that endoge nously produced TNF by monocytes had to be released and acted on TNF-R 2 on the monocyte surface. The enhancing effect of exogeneous TNF was also abrogated by anti-TNF-R2 mAb. Pretreatment of monocytes with rTNF enhanced, while pretreatment with PTX decreased, PPD-induced IL-6 pro duction. An increased production of IL-4 was found in cultures of PTX - treated, PPD-pulsed monocytes with T cells. This may indicate that i n the relative absence of monocyte costimulatory signal(s), probably I L-6, Th, cells are stimulated. These results indicate that TNF is invo lved in control of monocyte-mediated regulation of cytokine production by T cells.