Abnormalities of the cellular immune system are present in patients with myocarditis and DCM. For patients with DCM, immunohistological methods have been introduced for diagnosis of myocardial inflammation. Infiltration with lymphocytes and mononuclear cells as well as increased expression of cell adhesion molecules, are frequent phenomena in DCM. These findings support the hypothesis that the immune process is still active. Furthermore, activation of the humoral immune system with production of cardiac antibodies plays an important role in DCM. Several antibodies against cardiac structures have been detected in DCM patients - including antibodies that act against mitochondrial proteins, alpha- and beta-cardiac myosin heavy chain isoforms, the cardiac beta-receptor, the muscarinic acetylcholine receptor-2, and the sarcolemmal Na-K-ATPase. The functional significance of cardiac autoantibodies is under debate. It is possible that autoantibodies are formed as a consequence of inflammatory reactions to cellular destruction, in which case they should be regarded as an epiphenomenon. Cardiac autoantibodies, on the other hand, may likewise play an active role in the pathogenesis of DCM by triggering the disease process, or by contributing to development of myocardial contractile dysfunction. For certain antibodies, in-vitro data indicate a negative effect on cardiac performance. In myocarditis and DCM, heart-reactive cytotoxic auto-antibodies to the ADP/ATP carrier were found. These antibodies cross-react with the calcium channel of the cardiomyocytes. Purified antibodies obtained from DCM patients induce a negative inotropic effect in isolated rat cardiomyocytes by decreasing the calcium transients. Immunization of rodents against peptides derived from cardiovascular G-protein receptors induces morphological changes of myocardial tissue resembling DCM. Furthermore, recent data have provided evidence those antibodies against the beat1-receptor itself induce DCM: rats immunized against the second extracellular loop of cardiac beta1-receptors develop progressive left ventricular dilatation and dysfunction. Interestingly, sera transferred from these immunized animals to unsensitized rats induced the similar cardiomyopathic phenotype, thus demonstrating the pathogenic potential of a particular antibody for development of DCM. Further confirmation of the principle that autoantibodies contribute to induction of the disease process and to progression to DCM has been provided in a recent study. The authors showed that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory co-receptor develop autoimmune DCM with production of high-titre circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. This antigen was recently identified as cardiac troponin I.