Altered T cell signaling events caused by anti-CD4 monoclonal antibody in suppressing experimental autoimmune cardiomyopathy

AIM: We examined the efficacy of anti-L3T4 McAb in the T cell signaling pathway in treating experimental autoimmune cardiomyopathy in BALB/c mice,as a model of the autoimmune mechanism involved in human dilated cardiomyopathy(DCM).METHODS: ADP/ATP carrier peptides were used to induce autoimmune cardiomyopathy in BALB/c mice.After 3 months,anti-L3T4 McAb was administered to deplete CD4+ T cells in the mice.Real-time PCR were used to detect the expression of intracellular signaling molecules(p56lck,p59fyn and Zap-70) and cytokine production(IFN-γ,IL-2 and IL-4) in T cells.The expression of CD45 was determined by immunohistochemistry analysis.RESULTS: Reduced expression of p56lck,p59fyn and Zap-70 and the reduced cytokine production of IFN-γ,IL-2 and IL-4 in T cells of anti-L3T4-treated DCM mice were found.Also,the expression of CD45 in spleen T cells was significantly decreased in the anti-L3T4-treated group.In contrast,immunization with irrelevant Ab did not protect the mice,the expression of T cell signaling molecules,CD45,and cytokine were not inhibited.CONCLUSION: These studies provide direct evidence that anti-L3T4 McAb can be an effective immunomodulator to T cell signal molecules and subsequent cytokine production events in ADP/ATP carrier-induced DCM in BALB/c mice.