Analysis of IgG subclass antibodies and expression of T-Cell receptor signaling molecules in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy.
T-cell immune abnormality in patients of dilated cardiomyopathy has been intensively studied over the past 10 years. In this study, we aim to focus on the molecular mechanism of T-cells in autoimmune cardiomyopathy mouse model by detecting the expression of three T-cell signaling molecules. Balb/C mice (n = 12) were immunized with the peptides derived from human ADP/ATP carrier on the 1st, 14th, 28th, 49th and 79th days, and half of them were also injected with anti-L3T4 McAb on the - 1st, 0 and 1st days. The sham-immunized mice were taken as the controls (n = 6). The main result shows that the antibody response of IgG subclasses such as IgG1, IgG2b and IgG3 were definitely blocked except IgG2a in CD4+ cell-depleted Balb/C mice. In addition, the average mRNA expression of p56lck, p59fyn and zap-70 were all found to be dramatically higher in the mice immunized with only ADP/ATP carrier peptides than in the control-group. At meantime, reduced levels of the protein kinases p56lck, p59fyn and zap-70 were clearly observed in anti-CD4 McAb immunized group compared with DCM group. We propose that the proliferation of T-cells was significantly inhibited in anti-CD4 treated mice and CD4+ T-cells may play a critical role in ADP/ATP carrier caused mouse DCM.
Wang
Zhaohui
Z
Laboratory of Cardiovascular immunology, Tongji Medical College, Institute of Cardiology, Union Hospital, Huazhong Technology and Science University, 1277 Jie-Fang Avenue, Wuhan, 430022, People's Republic of China.
Liao
Yu-Hua
YH
Yuan
Jing
J
Zhang
Jing-Hui
JH
Liu
Zhong-Ping
ZP
Dong
Ji-Hua
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D049109:Cell Proliferation; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology; D010455:Peptides / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D000226:Mitochondrial ADP, ATP Translocases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse