The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation
| Autor: | Michael A. Nalesnik, Rita M. Sico, Matthew Zhang, Noriko Murase, Mark A. Ross, Shinya Ueki, Shoko Kimura, Kikumi S. Ozaki, Donna B. Stolz |
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| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Pathology Time Factors 030232 urology & nephrology Adaptive Immunity Kidney Rats Sprague-Dawley 0302 clinical medicine IFN-γ IFN-α 0303 health sciences CD11b Antigen IF/TA Flow Cytometry Chemotaxis Leukocyte Phenotype medicine.anatomical_structure Nephrology Reperfusion Injury CD103 Inflammation Mediators Rats Transgenic Integrin alpha Chains medicine.medical_specialty Green Fluorescent Proteins Ischemia Cold storage Biology Article Immunophenotyping Interferon-gamma 03 medical and health sciences effector CD4+ T cells Antigens CD medicine Animals Kidney surgery 030304 developmental biology Renal ischemia Tumor Necrosis Factor-alpha Dendritic Cells Dendritic cell medicine.disease Fibrosis Kidney Transplantation Immunity Innate CD11c Antigen Rats Transplantation Transplantation Isogeneic Gene Expression Regulation TNF-α Atrophy Immunologic Memory Reperfusion injury Biomarkers |
| Zdroj: | Kidney international |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2011.458 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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