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. The Journal of Immunology, 2009, 183: 984-992.