Effects of immunotherapy with anti-L3T4 monoclonal antibody on autoimmune cardiomyopathy: experiment with mice

Abstract

To evaluate the effects of immunotherapy with anti-L3T4 monoclonal antibody (McAb) on autoimmune cardiomyopathy. 24 male Balb/c mice were immunized with mitochondria ADP/ATP carrier peptides so as to establish a model of autoimmune cardiomyopathy, and then randomly divided into 4 equal groups: cardiomyopathy control group, early-treated group injected with anti-L3T4 McAb on the day before immunization, the very day of immunization, and 1 day after the immunization, mid-term-treated group, administrated with anti-L3T4 McAb on the 89th, 90th and 91st days after immunization, and sham-immunization control group, injected with solution without anti-L3T4 McAb. Six months after blood samples were collected. The serum antibodies against ADP/ATP carrier were examined with ELISA, and the expression of IFN-gamma and IL-4, T cell cytokines, in T cells were detected by 3-color flow cytometry. The myocardium underwent pathological examination by using light and electron microscopes. The bulk percentages of cardiac collagen fiber were calculated with computer. Antibodies against ADP/ATP carrier were negative in the early-treated group and the sham-immunization control group and positive in the mid-term-treated and cardiomyopathy groups with a transient decline in the mid-term-treated group. By the end of 6 month, there were no cardiac morphological and histopathological changes like those in dilated cardiomyopathy (DCM) in the early-treated group and sham-immunization group, while they were found in the mid-term-treated and cardiomyopathy groups with severer myocardial impairments in the cardiomyopathy group. The percentage of IFN-gamma/IL-4 of the early-treated group was 6.56% +/- 0.21%/2.54% +/- 0.20%, not significantly different from that of the control group (5.87% +/- 0.19%/2.16% +/- 0.10%), however, the values of these 2 groups were significantly higher than those of the mid-term-treated group (8.91% +/- 0.33%/5.15% +/- 0.13%, both P < 0.01) and the cardiomyopathy group (7.85% +/- 1.42%/9.45% +/- 1.70%, both P < 0.01). Anti-L3T4 McAb administration is effective on protection from autoimmune cardiomyopathy induced by mitochondria ADP/ATP carrier peptides, especially being used at the initial phase of this disease.