Protection of rats from adjuvant arthritis by immunization with naked DNA encoding for mycobacterial heat shock protein 65.
OBJECTIVE
To assess the feasibility of vaccination with naked DNA encoding for mycobacterial heat shock protein 65 (hsp65) in the modulation of experimental arthritis.


METHODS
Adjuvant arthritis (AA) was induced in Lewis rats preimmunized, intramuscularly, with a plasmid encoding for hsp65 (pCMV3.65). Clinical scores were recorded for 3-4 weeks, and histologic and radiologic parameters were evaluated. Cellular and antibody reactivity to hsp65 was assessed. The expression of the hsp65 gene was investigated in injected muscles.


RESULTS
The pCMV3.65-treated rats were significantly protected from disease development in comparison with the control groups. This finding correlated with the results of histologic and radiologic examinations of the involved joints. The message for hsp65 was detected in injected muscles. T cell proliferation and antibodies to this protein were found to be elevated in pCMV3.65-treated rats when compared with both the arthritic control (AA-induced) and the naive (did not receive adjuvant) animals.


CONCLUSIONS
We have demonstrated for the first time that naked DNA delivery is feasible in controlling experimental autoimmune disease. Although the actual mechanism of protection has not been fully elucidated, this simple and versatile approach could represent a useful tool in dissecting basic autoimmune mechanisms.
Ragno
S
S
Division of Mycobacterial Research, National Institute for Medical Research, London, UK.
Colston
M J
MJ
Lowrie
D B
DB
Winrow
V R
VR
Blake
D R
DR
Tascon
R
R
D000818:Animals; D000843:Ankle Joint / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D000917:Antibody Formation; D000942:Antigens, Bacterial; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000235:genetics; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics*; D004269:DNA, Bacterial / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D009132:Muscles / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D004269:DNA, Bacterial; D012333:RNA, Messenger; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins