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 R Hamad

Research output: Contribution to journalArticle


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 : JASN
Issue number4
StatePublished - Apr 1 2016



  • acute kidney injury
  • CD4−CD8−
  • double-negative T cells
  • human kidney
  • ischemia-reperfusion

ASJC Scopus subject areas

  • Nephrology

Cite this