Key result
Anti-CD4 monoclonal antibody treatment reduced P56lck and Zap-70 gene expression, lowered CD45 expression, and reversed the Th1/Th2 ratio in a mouse model of autoimmune cardiomyopathy.
Why the study?
Does anti-CD4 monoclonal antibody inhibit T cell receptor signal transduction in a mouse model of autoimmune cardiomyopathy?
Does anti-CD4 monoclonal antibody inhibit T cell receptor signal transduction in a mouse model of autoimmune cardiomyopathy?
Anti-CD4 monoclonal antibody effectively inhibits early T cell receptor signal transduction and autoantibody production in a mouse model of autoimmune dilated cardiomyopathy.
Hypothesis-generating for T-cell modulation in autoimmune cardiomyopathy models; leaves open translation to human dilated cardiomyopathy.
BACKGROUND: T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules. METHODS: The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n = 6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-gamma and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR. RESULTS: Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group. CONCLUSION: The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.
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Wang et al. (2007) studied Autoimmune cardiomyopathy. Anti-CD4 monoclonal antibody (Anti-L3T4) vs. Rat anti-mouse IgG (irrelevant antibody) was evaluated on Expression of T cell signaling molecules (P56lck, Zap-70), CD45, and Th1/Th2 ratio. Anti-CD4 monoclonal antibody treatment reduced P56lck and Zap-70 gene expression, lowered CD45 expression, and reversed the Th1/Th2 ratio in a mouse model of autoimmune cardiomyopathy.
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