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

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 : JASN
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

T-Lymphocytes
Kidney
Reperfusion Injury
Interleukin-10
Anti-Inflammatory Agents
Interleukin-27
CD40 Ligand
Natural Killer T-Cells
Adoptive Transfer
T-Lymphocyte Subsets
T-Cell Antigen Receptor
Cytokines
Population

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney. / Martina, Maria N.; Noel, Sanjeev; Saxena, Ankit; Bandapalle, Samatha; Majithia, Richa; Jie, Chunfa; Arend, Lois J; Allaf, Mohamad E; Rabb, Hamid; Hamad, Abdel R.

In: Journal of the American Society of Nephrology : JASN, Vol. 27, No. 4, 01.04.2016, p. 1113-1123.

Research output: Contribution to journalArticle

@article{19bc2a6bd77a4ef29fa8f5b0940c217c,
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.",
keywords = "acute kidney injury, CD4−CD8−, double-negative T cells, human kidney, ischemia-reperfusion",
author = "Martina, {Maria N.} and Sanjeev Noel and Ankit Saxena and Samatha Bandapalle and Richa Majithia and Chunfa Jie and Arend, {Lois J} and Allaf, {Mohamad E} and Hamid Rabb and Hamad, {Abdel R}",
year = "2016",
month = "4",
day = "1",
doi = "10.1681/ASN.2014121214",
language = "English (US)",
volume = "27",
pages = "1113--1123",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "4",

}

TY - JOUR

T1 - Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney

AU - Martina, Maria N.

AU - Noel, Sanjeev

AU - Saxena, Ankit

AU - Bandapalle, Samatha

AU - Majithia, Richa

AU - Jie, Chunfa

AU - Arend, Lois J

AU - Allaf, Mohamad E

AU - Rabb, Hamid

AU - Hamad, Abdel R

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - acute kidney injury

KW - CD4−CD8−

KW - double-negative T cells

KW - human kidney

KW - ischemia-reperfusion

UR - http://www.scopus.com/inward/record.url?scp=85017042209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017042209&partnerID=8YFLogxK

U2 - 10.1681/ASN.2014121214

DO - 10.1681/ASN.2014121214

M3 - Article

VL - 27

SP - 1113

EP - 1123

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 4

ER -