Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemicrabbits 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 mycoba cterial heat shock protein (hsp) 65. To further investigate the immunologic mechanisms underlying such vascular lesions, 39 male New Zealand White rab bits were treated by triple immunization with fortified Freund's complete a djuvant 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 prednisolon e (1 mg/kg) alone. Sixteen weeks after the first immunization the animals w ere 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 mo noclonal antibody and prednisolone treatment showed a single moderate lesio n in the aorta, whereas 5 of 9 rabbits immunized and immunosuppressed by pr ednisolone treatment alone showed lesions, albeit mild. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunizati on with hsp65 can be inhibited by immunosuppressive therapy with anti-CD3 m onoclonal antibody.