The role for T cell repertoire/antigen-specific interactions in experimental kidney ischemia reperfusion injury.
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.
Satpute
Shailesh Ramchandra
SR
Department of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Park
Jong Myun
JM
Jang
Hye Ryoun
HR
Agreda
Patricia
P
Liu
Manchang
M
Gandolfo
Maria Teresa
MT
Racusen
Lorraine
L
Rabb
Hamid
H
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
D018984:Epitopes, T-Lymphocyte