title: Novel CD8 T cell alloreactivities in CCR5-deficient recipients of class II MHC disparate kidney grafts.
abstract: Recipient CD4 T regulatory cells inhibit the acute T cell-mediated rejection of renal allografts in wild-type mice. The survival of single class II MHC-disparate H-2(bm12) renal allografts was tested in B6.CCR5(-/-) recipients, which have defects in T regulatory cell activities that constrain alloimmune responses. In contrast to wild-type C57BL/6 recipients, B6.CCR5(-/-) recipients rejected the bm12 renal allografts. However, donor-reactive CD8 T cells rather than CD4 T cells were the primary effector T cells mediating rejection. The CD8 T cells induced to bm12 allografts in CCR5-deficient recipients were reactive to peptides spanning the 3 aa difference in the I-A(bm12) versus I-A(b) β-chains presented by K(b) and D(b) class I MHC molecules. Allograft-primed CD8 T cells from CCR5-deficient allograft recipients were activated during culture either with proinflammatory cytokine-stimulated wild-type endothelial cells pulsed with the I-A(bm12) peptides or with proinflammatory cytokine-simulated bm12 endothelial cells, indicating their presentation of the I-A(bm12) β-chain peptide/class I MHC complexes. In addition to induction by bm12 renal allografts, the I-A(bm12) β-chain-reactive CD8 T cells were induced in CCR5-deficient, but not wild-type C57BL/6, mice by immunization with the peptides. These results reveal novel alloreactive CD8 T cell specificities in CCR5-deficient recipients of single class II MHC renal allografts that mediate rejection of the allografts.
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Urology, Kitasato University, Kanagawa 228-8555, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ishii
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Rosenblum
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195;
authors.forename: Taiji
authors.initials: T
authors.lastname: Nozaki
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and.
authors.forename: Austin D
authors.initials: AD
authors.lastname: Schenk
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195;
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Setoguchi
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Su
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195;
authors.forename: Victoria
authors.initials: V
authors.lastname: Gorbacheva
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and Glickman Urological Institute and the Transplant Center, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and Glickman Urological Institute and the Transplant Center, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: Anna
authors.initials: A
authors.lastname: Valujskikh
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and Glickman Urological Institute and the Transplant Center, Cleveland Clinic, Cleveland, OH 44195 fairchr@ccf.org.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D064591:Allografts; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D016030:Kidney Transplantation; D051379:Mice; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D019713:Receptors, CCR5