Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemic rabbits immunized with heat shock protein 65.
Previous studies in our laboratory have shown that arteriosclerotic changes can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein (hsp) 65. To further investigate the immunologic mechanisms underlying such vascular lesions, 39 male New Zealand White rabbits were treated by triple immunization with fortified Freund's complete adjuvant containing 5 mg/mL Mycobacterium tuberculosis as a source of hsp65 and simultaneous immunosuppressive therapy twice per week with either anti-CD3 monoclonal antibody (1 mg/kg) and prednisolone (1 mg/kg) or prednisolone (1 mg/kg) alone. Sixteen weeks after the first immunization the animals were killed, and as expected, severe arteriosclerotic lesions in the intima of the aortic arch were found in 9 of 10 immunized rabbits. However, only 1 of 10 rabbits immunized and immunosuppressed with the combined anti-CD3 monoclonal antibody and prednisolone treatment showed a single moderate lesion in the aorta, whereas 5 of 9 rabbits immunized and immunosuppressed by prednisolone treatment alone showed lesions, albeit mild. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp65 can be inhibited by immunosuppressive therapy with anti-CD3 monoclonal antibody.
Metzler
B
B
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Institute for General and Experimental Pathology, University of Innsbruck Medical School, Innsbruck, Austria.
Mayr
M
M
Dietrich
H
H
Singh
M
M
Wiebe
E
E
Xu
Q
Q
Wick
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001161:Arteriosclerosis / Q000473:pathology*; D001426:Bacterial Proteins; D001786:Blood Glucose / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002469:Cell Separation; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D002784:Cholesterol / Q000097:blood*; D005434:Flow Cytometry; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D011241:Prednisone / Q000494:pharmacology; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D001786:Blood Glucose; D017252:CD3 Complex; D018834:Chaperonin 60; D007166:Immunosuppressive Agents; C074119:heat-shock protein 65, Mycobacterium; D002784:Cholesterol; D018833:Chaperonins; D011241:Prednisone