Double-negative αβ T cells are early responders to AKI and are found in human kidney

Maria N. Martina, Sanjeev Noel, Ankit Saxena, Samatha Bandapalle, Richa Majithia, Chunfa Jie, Lois J. Arend, Mohamad E. Allaf, Hamid Rabb, Abdel Rahim A. Hamad

Research output: Contribution to journalArticlepeer-review

Abstract

Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4+ T cells, natural killer T cells, and CD4+CD25+FoxP3+ Tregs in AKI pathogenesis. We recently identified CD4-CD8- (double-negative; DN) T cells as an important subset of αβ T cell receptor–positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4+ and CD8+ T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4+ T cells. Within the first 3–24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10–dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ+ T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.

Original languageEnglish (US)
Pages (from-to)1113-1123
Number of pages11
JournalJournal of the American Society of Nephrology
Volume27
Issue number4
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Nephrology

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