Cardiac impairments induced by adoptive transfer of lymphocytes from the experimental cardiomyopathy in mice

Abstract

To investigate the autoimmune mechanism in dilated cardiomyopathy (DCM). Thirty-six male Balb/c mice were randomly divided into 2 groups: DCM group to be immunized with human mitochondrion ADP/ATP vector polypeptides and control group (sham immunization group) to be injected with immune fluid without the polypeptide. Before the injection and then every month after the injection serum was collected to examine the ADP/ATP autoantibody level by ELISA. One month after immunization 6 mice of each group were killed and 6 months after the remaining mice were all killed to undergo serologic and histological examination. Lymphocytes from spleen were collected from the mice injected with ADP/ATP vector polypeptides, some of these spleen lymphocytes were co-cultured with concanavalin A (ConA) and some were cultured without stimulation of ConA. Six months after the ADP/ATP vector polypeptide injection another 24 Balb/c mice were randomly divided into 2 groups: DCM-T-A group to be injected with the spleen lymphocytes stimulated by ConA and DCM-T group to be injected with the spleen lymphocytes without ConA stimulation. One month after the transfer 6 mice of each group were killed and 6 months after the remaining mice were all killed to undergo serologic and histological examination. One month and 6 months after immunization autoantibody against ADP/ATP vector was positive in the sera of the mice in both DCM and DCM-T-A groups. One month after immunization or transfer the myocardium of both DCM and DCM-T-A groups showed myocarditis-like changes, and 6 months after immunization or transfer the myocardium of both DCM and DCM-T-A groups showed DCM-like changes. Increase of different cytokines was found in the myocardium in both DCM and DCM-T-A groups with predominance of interferon-gamma and interleukin (IL)-2 one month after and predominance of IL-4, IL-6, and tumor necrosis factor-alpha 6 months after immunization or transfer. Such changes were not found in the control group and DCM-T group. Human mitochondria ADP/ATP peptides induce autoimmune DCM in mice. T cell-mediated responses play an important role in the development of DCM.