Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis.
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| Abstract |
The class of immune response against autoantigens could profoundly influence the onset and/or outcome of autoimmune diseases. Until now, there is only limited information on the antigen-specific balance between proinflammatory and regulatory responses in humans. Here we analyzed the natural immune response against a candidate autoantigen in rheumatoid arthritis, human cartilage glycoprotein-39 (HC gp-39). Peripheral blood mononuclear cells from healthy individuals reacted against HC gp-39 with the production of IL-10 but not IFN-gamma. Ex vivo assays indicated that the naturally occurring HC gp-39-specific immune response in bulk is powerful enough to suppress antigen-specific recall responses, demonstrating that rather than being unresponsive, the HC gp-39-directed immune response in healthy individuals shows a strong bias toward a regulatory phenotype. Moreover, CD4(+) T cell lines directed against HC gp-39 expressed CD25, glucocorticoid-induced tumor necrosis factor receptor, and Foxp3 molecules and were capable of suppressing antigen-specific T cell responses. Cell-cell contact was required for this suppression. As opposed to healthy individuals, the HC gp-39-directed immune response in 50% of patients with rheumatoid arthritis exhibits polarization toward a proinflammatory T helper 1 phenotype and is significantly less powerful in suppressing antigen-specific recall responses. Together these findings indicate that the presence of HC gp-39-specific immune responses in healthy individuals may have an inhibitory effect on inflammatory responses in areas where HC gp-39 is present. Furthermore, these data indicate that the class of HC gp-39-directed immune response in rheumatoid arthritis patients has shifted from an antiinflammatory toward a proinflammatory phenotype.
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| Authors | Jolanda H M van Bilsen, Henrike van Dongen, Leroy R Lard, Ellen I H van der Voort, Diënne G Elferink, Aleida M Bakker, André M M Miltenburg, Tom W J Huizinga, René R P de Vries, René E M Toes |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 49 Pg. 17180-5 (Dec 07 2004) ISSN: 0027-8424 [Print] United States |
| PMID | 15569925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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