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Analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy

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Summary

The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6–8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P<0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P<0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.

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Zhaohui WANG, female, born in 1969, M.D., Ph.D

This project was supported by a grant from the National Natural Science Foundation of China (No. 30000070).

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Wang, Z., Liao, Y., Yuan, J. et al. Analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 409–414 (2008). https://doi.org/10.1007/s11596-008-0408-y

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  • DOI: https://doi.org/10.1007/s11596-008-0408-y

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