Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney

J Am Soc Nephrol. 2016 Apr;27(4):1113-23. doi: 10.1681/ASN.2014121214. Epub 2015 Aug 27.


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.

Keywords: CD4−CD8−; acute kidney injury; double-negative T cells; human kidney; ischemia-reperfusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / immunology*
  • Animals
  • CD4 Antigens
  • CD8 Antigens
  • Humans
  • Kidney / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / physiology*


  • CD4 Antigens
  • CD8 Antigens