Heat shock protein 65-reactive T cells are involved in the pathogenesis of non-antigenic dimethyl dioctadecyl ammonium bromide-induced arthritis.
Dimethyl dioctadecyl ammonium bromide (DDA) (C(38)H(80)NBr) is a nonantigenic lipoid material. DDA-induced arthritis (DIA) in the Lewis (LEW) (RT.1(l)) rat is a new experimental model for human rheumatoid arthritis (RA). DIA is a T cell-mediated autoimmune disease. However, the precise self/foreign Ags associated with the disease process in DIA are not yet known. We observed that LEW rats with DIA spontaneously raised a vigorous T cell response both to 65-kDa self (rat) heat shock protein (Rhsp65) and mycobacterial hsp65 (Bhsp65), but not to another arthritis-related Ag, bovine collagen type II. The T cell response to Rhsp65 was focused predominantly on determinant regions 120-134 and 213-227 of the self protein. Interestingly, pretreatment of adult LEW rats using either a mixture of peptides 120-134 and 213-227 of Rhsp65 or a low nonarthritogenic dose of DDA induced protection against subsequent DIA. Intriguingly, the protection induced by the latter was associated with spontaneous priming of T cells specific for peptide 213-227 of Rhsp65. Similarly, LEW rats neonatally tolerized against either Rhsp65 or Bhsp65 were significantly protected from subsequently induced DIA at adult stage, showing the disease-modulating attribute of the hsp65-specific T cells. Taken together, the above findings demonstrate that the hsp65-directed T cell repertoire is of significance in the pathogenesis of autoimmune arthritis induced by nonantigenic DDA. Like other animal models of RA involving hsp65, these first insights into the disease-associated Ags in the DIA model would pave the way for further understanding of the immunological aspects of induction and regulation of RA.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Md Younus
MY
Mia
Malarvizhi
M
Durai
Hong Ro
HR
Kim
Kamal D
KD
Moudgil
D000818:Animals; D000831:Animals, Newborn; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage; D001426:Bacterial Proteins / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000008:administration & dosage; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D024043:Collagen Type II; D000939:Epitopes; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D000644:Quaternary Ammonium Compounds; C074119:heat-shock protein 65, Mycobacterium; C015831:dimethyldioctadecylammonium; D018833:Chaperonins