EXPERIMENTAL AUTOIMMUNE MYOCARDITIS PRODUCED BY ADOPTIVE TRANSFER OF SPLENOCYTES AFTER MYOCARDIAL-INFARCTION

One possible mechanism for neurohumoral activation alter myocardial in farction may be the generation of an immune response against cardiac s elf-antigens. We hypothesize that if there is a T cell-mediated reacti on to self-antigens, the transfer of splenic lymphocytes hom postinfar ct rats into syngeneic rats with normal hearts should result in a T ce ll-mediated autoimmune myocarditis in the healthy syngeneic rats. Rats were killed 6 weeks after coronary ligation. Splenocytes from animals with large and small infarcts were purified from spleens, activated w ith concanavalin A, and injected in varying doses into normal syngenei c rats. These recipient rats were killed 6 weeks later, and histopatho logical studies were performed. Our results demonstrate in vivo eviden ce of lymphocyte-mediated myocardial injury by adoptive transfer of se nsitized lymphocytes from rats who developed congestive heart failure after acute myocardial infarction. The amount of infiltrate and necros is in the recipient rats appeared directly related to the size of the infarct from the donor rats. This suggests that larger infarcts lead t o a greater inflammatory response as well as a greater propensity for alteration of cardiac surface antigens or the emergence of previously sequestered antigens. None of the other organs (kidney, liver, lung, o r brain) had evidence of infiltrates. Two-dimensional echocardiography did not reveal systolic dysfunction. This study provides direct evide nce of autoimmune myocardial injury produced by adoptive transfer of c oncanavalin A-activated splenocytes after myocardial infarction. We pr opose that neurohumoral activation early in the postinfarction period triggers a series of specific inflammatory and immunological events th at lead to formation of specific clones of T cells. When these are act ivated and transferred into normal rats, cardiac-specific cellular inf iltration occurs, occasionally accompanied by myocardial necrosis. Thi s model should help to further explore the link between neurohumoral a ctivation after myocardial infarction and the subsequent immune altera tions that might be associated with the development and/or progression of congestive heart failure. Additionally, this might be a useful mod el in which to study other immune-mediated cardiomyopathies.