title: Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney.
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.
authors: Department of Pathology.
authors: Maria N
authors: MN
authors: Martina
authors: Department of Medicine, and.
authors: Sanjeev
authors: S
authors: Noel
authors: Department of Pathology.
authors: Ankit
authors: A
authors: Saxena
authors: Department of Medicine, and.
authors: Samatha
authors: S
authors: Bandapalle
authors: Department of Pathology.
authors: Richa
authors: R
authors: Majithia
authors: Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Chunfa
authors: C
authors: Jie
authors: Department of Pathology.
authors: Lois J
authors: LJ
authors: Arend
authors: Department of Urology, Johns Hopkins University, Baltimore, Maryland, and.
authors: Mohamad E
authors: ME
authors: Allaf
authors: Department of Medicine, and hrabb1@jhmi.edu.
authors: Hamid
authors: H
authors: Rabb
authors: Department of Pathology.
authors: Abdel Rahim A
authors: AR
authors: Hamad
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens; D016827:CD8 Antigens; D006801:Humans; D007668:Kidney / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens
keywords: CD4−CD8−; acute kidney injury; double-negative T cells; human kidney; ischemia-reperfusion