Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-gamma.
The pathogenesis of T cell-mediated diseases like rheumatoid arthritis (RA) has typically been explained in the context of the Th1-Th2 paradigm: the initiation/propagation by pro-inflammatory cytokines, and downregulation by Th2 cytokines. However, in our study based on the adjuvant-induced arthritis (AA) model of RA, we observed that Lewis (LEW) (RT.1(l)) rats at the recovery phase of AA showed the highest level of IFN-gamma in recall response to mycobacterial heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1(l)) rats secreted high levels of IFN-gamma much earlier following disease induction. However, no significant secretion of IL-10 or TGF-beta was observed in either strain. Furthermore, pre-treatment of LEW rats with a peptide of self (rat) hsp65 (R465), which induced T cells secreting predominantly IFN-gamma, afforded protection against AA and decreased IL-17 expression by the arthritogenic epitope-restimulated T cells. These results provide a novel perspective on the pathogenesis of autoimmune arthritis.
Kim
Eugene Y
EY
Department of Microbiology and Immunology, University of Maryland School of Medicine, HH 323C, 660 W. Redwood St., Baltimore, MD 21201, USA.
Chi
Howard H
HH
Bouziane
Mohammed
M
Gaur
Amitabh
A
Moudgil
Kamal D
KD
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma; D018833:Chaperonins