title: The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.
abstract: Ischemia/reperfusion injury associated with kidney transplantation induces profound acute injury, influences early graft function, and affects long-term graft outcomes. To determine whether renal dendritic cells play any role during initial innate ischemia/reperfusion injury and the subsequent development of adaptive immune responses, we studied the behavior and function of renal graft and host infiltrating dendritic cells during early and late phases of renal ischemia/reperfusion injury. Wild type to green fluorescent protein (GFP) transgenic rat kidney transplantation was performed with and without 24-h cold storage. Ischemia/reperfusion injury in cold-stored grafts resulted in histopathological changes of interstitial fibrosis and tubular atrophy by 10 weeks, accompanied by upregulation of mRNAs of mediators of interstitial fibrosis and inflammation. In normal rat kidneys, we identified two populations of renal dendritic cells, predominant CD103(-)CD11b/c(+) and minor CD103(+)CD11b/c(+) cells. After transplantation without cold storage, grafts maintained CD103(-) but not CD103(+) GFP-negative renal dendritic cells for 10 weeks. In contrast, both cell subsets disappeared from cold-stored grafts, which associated with a significant GFP-expressing host CD11b/c(+) cell infiltration that included CD103(+) dendritic cells with a TNF-α-producing phenotype. These changes in graft/host dendritic cell populations were associated with progressive infiltration of host CD4(+) T cells with effector/effector-memory phenotypes and IFN-γ secretion. Thus, renal graft ischemia/reperfusion injury caused graft dendritic cell loss and was associated with progressive host dendritic cell and T-cell recruitment. Renal-resident dendritic cells might function as a protective regulatory network.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Kikumi S
authors.initials: KS
authors.lastname: Ozaki
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalesnik
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Sico
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ross
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: murase@pitt.edu.
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005355:Fibrosis; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D039481:CD11b Antigen; D039521:CD11c Antigen; D018836:Inflammation Mediators; D039001:Integrin alpha Chains; D014409:Tumor Necrosis Factor-alpha; C091367:alpha E integrins; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma