Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls.
IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.
Lenarczyk
A
A
Department of Rheumatology, St George Hospital, Kogarah, Australia.
Helsloot
J
J
Farmer
K
K
Peters
L
L
Sturgess
A
A
Kirkham
B
B
D000328:Adult; D000368:Aged; D000485:Allergens; D052179:Antigens, Plant; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006304:Health Status; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D010940:Plant Proteins / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger; D013745:Tetanus Toxoid / Q000276:immunology* / Q000494:pharmacology; D014373:Tuberculin / Q000276:immunology* / Q000494:pharmacology
D000485:Allergens; D052179:Antigens, Plant; D020381:Interleukin-17; C042814:Lol p I protein, Lolium perenne; D008934:Mitogens; D010940:Plant Proteins; D012333:RNA, Messenger; D013745:Tetanus Toxoid; D014373:Tuberculin