title: Increased expression of CCR5 in experimental autoimmune myocarditis and reduced severity induced by anti-CCR5 monoclonal antibody.
abstract: Experimental autoimmune myocarditis (EAM) is a T-cell-mediated autoimmune disease. CCR5, which is expressed mostly on activated T cells and monocytes/macrophages, are potent chemotactic factors for autoimmune myocarditis. We investigated the role of CCR5 in the formation of experimental autoimmune myocarditis. Expression of CCR5 and its cognate ligands was assessed by RT-PCR and immunohistochemical analysis. Single-cell suspension of splenocytes and whole blood specimens from EAM mice were subjected to flow-cytometry analysis. We investigated the critical role of CCR5 in EAM mice by adoptively transferring CCR5-positive/negative T cells to mice and by neutralizing CCR5 with monoclonal antibody to observe the influence on the severity and prevalence of myocarditis. In this report, we found that CCR5-positive cells predominate in infiltrated inflammatory cells in cardiac tissue of EAM mice and CCR5-positive T cells in peripheral blood increased markedly in EAM mice compared with controls. Moreover, we demonstrated that the severity of myocarditis was significantly reduced when CCR5-negative T cells from EAM mice were adoptively transferred. When administrated with CCR5-positive T cells, the myocarditis was significantly aggravated. We also demonstrated that blockade of CCR5 with monoclonal antibodies significantly reduced severity of myocarditis in EAM mice. Overall, these findings indicate that CCR5 is important in the induction of EAM and inhibition of CCR5 with monoclonal antibody significantly reduces the severity of myocarditis. CCR5 may have the potential to become a new therapy target against autoimmune myocarditis.
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Gong
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.forename: Shuying
authors.initials: S
authors.lastname: Zhang
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.forename: Jvrong
authors.initials: J
authors.lastname: Wang
authors.forename: Baoyu
authors.initials: B
authors.lastname: Guo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D065100:CCR5 Receptor Antagonists; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009205:Myocarditis / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D065100:CCR5 Receptor Antagonists; D016207:Cytokines; D012333:RNA, Messenger; D019713:Receptors, CCR5