The dynamics of articular leukocyte trafficking and the immune response to self heat-shock protein 65 influence arthritis susceptibility.
BACKGROUND
Adjuvant arthritis (AA) shares several features with human rheumatoid arthritis, and it can be induced in the Lewis (LEW) rat but not the Wistar Kyoto (WKY) rat (both RT.1(l)) by immunization with heat-killed Mycobacterium tuberculosis (Mtb). We set out to unravel the mechanisms underlying the differential susceptibility to AA of these MHC-compatible rat strains.


METHODS
We compared the levels of T-cell proliferative and cytokine response to the immunoregulatory self (rat) hsp65 (Rhsp65) after an arthritogenic (Mtb) challenge and the kinetics of migration of adoptively transferred, (111)Indium-labeled, Mtb-primed leukocytes into the hind paw joints of recipient rats.


CONCLUSIONS
The WKY rats raised a significantly higher level of T-cell proliferative response coupled with a temporally opposite cytokine profile against the disease-regulating Rhsp65 compared to that of LEW rats. Moreover, the arthritogenic leukocytes accumulated into the joints of WKY rats at significantly lower numbers than that in LEW rats.


CONCLUSIONS
These results offer novel insights into the immune events influencing the pathogenesis of autoimmune arthritis.
Mia
Md Y
MY
Department of Microbiology and Immunology, University of Maryland School of Medicine, Howard Hall 323C, 660 West Redwood Street, Baltimore, MD 21201, USA.
Kim
Eugene Y
EY
Satpute
Shailesh R
SR
Moudgil
Kamal D
KD
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002358:Cartilage, Articular / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007108:Immune Tolerance; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D013045:Species Specificity
D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D006360:Heat-Shock Proteins; D006649:Histocompatibility Antigens; C074119:heat-shock protein 65, Mycobacterium; C038353:histocompatibility antigens RT, rat; D018833:Chaperonins