IMPAIRMENT OF LEFT-VENTRICULAR FUNCTION IN COMBINED IMMUNE-DEFICIENCYMICE AFTER TRANSFER OF PERIPHERAL-BLOOD LEUKOCYTES FROM PATIENTS WITHMYOCARDITIS

Autoimmune mechanisms are suspected to play an important role in the p athogenesis of human myocarditis. In order to evaluate the significanc e of autoimmune leukocytes for the development of human myocarditis (M C) and subsequent heart failure we transferred 15 x 10(6) or 50 x 10(6 ) peripheral blood leukocytes (PBLs) from patients with immunohistolog ically proven MC and impaired left ventricular function into severe co mbined immune deficiency (SCID) mice that possess neither B nor T lymp hocytes. PBLs from seven patients and five healthy controls were trans ferred into three SCID mice each by intraperitoneal injection. After 6 0 days human PBLs could be demonstrated in the peripheral blood of SCI D mice, representing Icp to 10% of peripheral blood mononuclear cells. Likewise, human immunoglobulins were present in all transfused SCID m ice (up to 3 mg.ml(-1) IgG and IgM); however, autoantibodies against t he adenine nucleotide translocator, a myocardial autoantigen, were onl y present in the mice receiving PBLs from patients with MC. infiltrati ng human lymphocytes were also only found in the hearts of SCID mice h aving received PBLs from MC patients, but not in those receiving PBLs from normal controls. When we measured the slope of the left ventricul ar pressure pulse by direct puncture under ether anaesthesia, we found it to be decreased (dp/dt = 1750 +/- 194 mmHg.s(-1)) in mice receivin g PBLs from MC patients, compared with mice receiving PBLs from contro ls (dp/dt = 2456 +/- 92 mmHg.s(-1)) or receiving no transfusion (dp/dt = 2576 +/- 142 mmHg.s(-1)). These results demonstrate that the impair ment of the ventricular function seen in patients with IMC can be tran sferred to SCID mice by transfer of PBLs. This proves the significance of autoimmune mechanisms for the pathogenesis of MC.