MODULATION OF MONOCYTE ANTIGEN-PRESENTING CAPACITY BY TUMOR-NECROSIS-FACTOR-ALPHA (TNF) - OPPOSING EFFECTS OF EXOGENOUS TNF BEFORE AND AFTER AN ANTIGEN PULSE AND THE ROLE OF TNF GENE ACTIVATION IN MONOCYTES

We have previously shown that exogenous human recombinant tumour necro sis factor-alpha (rTNF), added before an antigen pulse, enhanced antig en presentation by human blood monocytes. The present study shows that , surprisingly, rTNF added after an antigen (PPD) pulse inhibited, whi le anti-TNF monoclonal antibody (mAb) enhanced, antigen presentation. mAbs htr-9 against p55 TNF receptor type I (TNF-RI) abrogated rTNF enh ancing effect on PPD presentation and decreased presenting activity of untreated monocytes while utr-1 mAb, against p75 TNF receptor type II (TNF-RII), reversed the inhibitory effect of rTNF given after antigen pulse. PPD and rTNF when added singly induced TNF-mRNA accumulation i n monocytes. Pretreatment of monocytes with rTNF followed by a PPD pul se caused an enhancement of TNF-mRNA accumulation. However, when post- treatment with rTNF was applied to PPD-pulsed monocytes, then inhibiti on of TNF gene expression was seen. This may point to the role of endo genously generated TNF in regulation of antigen-presenting capacity of monocytes. These studies indicate that TNF is an important regulator of monocyte antigen-presenting capacity and that the level of TNF gene activation in monocytes may be associated with their ability to prese nt nominal antigen.