Analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy.
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-gamma and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-gamma, 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.
Wang
Zhaohui
Z
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. sgwangtjm@163.com
Liao
Yuhua
Y
Yuan
Jing
J
Zhang
Jinghui
J
Dong
Jihua
J
Wang
Jinping
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000628:therapy; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology; D010455:Peptides / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D010455:Peptides; D000226:Mitochondrial ADP, ATP Translocases