title: Autoantibodies to vimentin cause accelerated rejection of cardiac allografts.
abstract: Autoimmune responses to vimentin occur after solid organ transplantation, but their pathogenic effects are unclear. The aim of these studies was to investigate the effects of vimentin preimmunization on allogeneic and isografted hearts in a murine transplant model. Immunization of C57BL/6 mice with murine vimentin in complete Freund's adjuvant resulted in anti-vimentin antibodies and vimentin-reactive Th-1 cells. Transplantation of 129/sv hearts into vimentin-immunized C57BL/6 recipients resulted in accelerated rejection (8.4 +/- 1.5 days; n = 18), compared with hen egg lysozyme-immunized C57BL/6 (13.3 +/- 2.2 days; n = 10; P < 0.0001, log-rank test). In contrast, isografts continued to beat beyond 90 days. Immunohistochemical analysis of allografts from vimentin/complete Freund's adjuvant mice demonstrated increased numbers of T cells and enhanced microvascular deposition of C3d, CD41, and P-selectin compared with controls. Antibodies were necessary for accelerated rejection, shown by the fact that vimentin-immunized B-cell-deficient IgH6 mice did not show accelerated rejection of 129/sv allografts, but rejection was restored by adoptive transfer of serum containing anti-vimentin antibodies. Eluates from donor hearts placed in vimentin/complete Freund's adjuvant recipients contained anti-vimentin antibodies, shown by Western blotting. Confocal imaging of rejected hearts de-monstrated presence of vimentin and C3d on apoptosed leukocytes, endothelial cells, and platelet/leukocyte conjugates. These results demonstrate that autoantibodies to vimentin, in conjunction with the alloimmune response, have a pathogenic role in allograft rejection.
authors: Imperial College, Heart Science Centre, Harefield Hospital, Harefield, UB9 6JH, UK.
authors: Balakrishnan
authors: B
authors: Mahesh
authors: Hon-Sing
authors: HS
authors: Leong
authors: Ann
authors: A
authors: McCormack
authors: Padmini
authors: P
authors: Sarathchandra
authors: Angela
authors: A
authors: Holder
authors: Marlene L
authors: ML
authors: Rose
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014611:Vaccination / Q000379:methods; D014746:Vimentin / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D007143:Immunoglobulin Heavy Chains; D007518:Isoantibodies; D014746:Vimentin