Modulation of monocyte antigen-presenting capacity by tumour 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 necrosis factor-alpha (rTNF), added before an antigen pulse, enhanced antigen presentation by human blood monocytes. The present study shows that, surprisingly, rTNF added after an antigen (PPD) pulse inhibited, while anti-TNF monoclonal antibody (mAb) enhanced, antigen presentation. mAbs htr-9 against p55 TNF receptor type I (TNF-RI) abrogated rTNF enhancing 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 in monocytes. Pretreatment of monocytes with rTNF followed by a PPD pulse caused an enhancement of TNF-mRNA accumulation. However, when post-treatment with rTNF was applied to PPD-pulsed monocytes, then inhibition of TNF gene expression was seen. This may point to the role of endogenously 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 present nominal antigen.
Kowalczyk
D
D
Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Cracow.
Mytar
B
B
Jasiński
M
M
Pryjma
J
J
Zembala
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014373:Tuberculin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha