title: The role for T cell repertoire/antigen-specific interactions in experimental kidney ischemia reperfusion injury.
abstract: T cells have been implicated in the early pathogenesis of ischemia reperfusion injury (IRI) of kidney, liver, lung, and brain. It is not known whether Ag-TCR engagement followed by Ag-specific T cell activation participates in IRI. T cell-deficient nu/nu mice are moderately resistant to renal IRI, which can be reversed upon reconstitution with syngeneic T cells. In this study, we found that nu/nu mice reconstituted with DO11.10 T cells, limited in their TCR repertoire, have significantly less kidney dysfunction and tubular injury after renal IRI compared with that in nu/nu mice reconstituted with wild-type T cells having a diverse TCR repertoire. CD4(+) T cells infiltrating ischemic kidneys of nu/nu mice reconstituted with DO11.10 T cells exhibited lower IFN-gamma production than that of wild-type controls. Frequency of regulatory T cells in kidneys of these mice was similar in both DO11.10 T cells and wild-type T cell recipient groups. DO11.10 mice immunized with OVA-CFA had significantly worse kidney function at 24 h after ischemia than those immunized with CFA alone. Thus, without T cell activation, diverse TCR repertoire was important for renal IRI in naive mice. However, once T cells were activated in an Ag-specific manner through TCR in DO11.10 mice, a restricted TCR repertoire no longer limited the extent of kidney injury. Thus, both TCR repertoire-dependent and -independent factors mediate T cell functions in kidney IRI.
authors: Department of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Shailesh Ramchandra
authors: SR
authors: Satpute
authors: Jong Myun
authors: JM
authors: Park
authors: Hye Ryoun
authors: HR
authors: Jang
authors: Patricia
authors: P
authors: Agreda
authors: Manchang
authors: M
authors: Liu
authors: Maria Teresa
authors: MT
authors: Gandolfo
authors: Lorraine
authors: L
authors: Racusen
authors: Hamid
authors: H
authors: Rabb
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007674:Kidney Diseases / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
chemical_list: D018984:Epitopes, T-Lymphocyte