The role for T cell repertoire/antigen-specific interactions in experimental kidney ischemia reperfusion injury

Shailesh Ramchandra Satpute, Jong Myun Park, Hye Ryoun Jang, Patricia Agreda, Manchang Liu, Maria Teresa Gandolfo, Lorraine Racusen, Hamid Rabb

Research output: Contribution to journalArticle

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-γ 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.

Original languageEnglish (US)
Pages (from-to)984-992
Number of pages9
JournalJournal of Immunology
Volume183
Issue number2
DOIs
StatePublished - Jul 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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