title: Antibody-mediated rejection of single class I MHC-disparate cardiac allografts.
abstract: Murine CCR5(-/-) recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2(b)) and B6.CCR5(-/-) recipients. Donor-specific antibody titers in CCR5(-/-) recipients were 30-fold higher than in wild-type recipients. B6.K(d) allografts survived longer than 60 days in wild-type recipients whereas CCR5(-/-) recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils and macrophages, and C4d deposition in the graft capillaries. B6.K(d) allografts were rejected by CD8(-/-)/CCR5(-/-), but not μMT(-/-)/CCR5(-/-), recipients indicating the need for antibody but not CD8 T cells. Grafts recovered at day 10 from CCR5(-/-) and CD8(-/-)/CCR5(-/-) recipients and from RAG-1(-/-) allograft recipients injected with anti-K(d) antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of antidonor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: R P
authors.initials: RP
authors.lastname: Bucy
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: W M
authors.initials: WM
authors.lastname: Baldwin
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin / Q000235:genetics; D009195:Peroxidase / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D019713:Receptors, CCR5; D054353:Perforin; D009195:Peroxidase