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 Rahim A.

doi:10.1681/asn.2014121214

Cited by 74 publications

(94 citation statements)

References 33 publications

(36 reference statements)

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“…DN T cells are rare in the peripheral blood and lymphoid organs but comprise a significant component of renal T cells accounting for 18 to 32% of resident T cells in both mouse and humans [25]. Renal DN T cells expand significantly in early phase of AKI, express higher level of IL-10 and IL-27 compared to conventional T lymphocytes, and adoptive transfer of DN T cells reduce ischemic AKI in mice.…”

Section: Immune Cells In Aki Repairmentioning

confidence: 99%

Role of Immune Cells in Acute Kidney Injury and Repair

Lee¹,

Noel²,

Sadasivam

et al. 2017

Nephron

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Acute kidney injury (AKI) is a significant problem in both native and transplant kidneys. There have been significant advances in understanding the role of immune cells in the early injury and repair from AKI. In this brief review, we aim to update information on the pathophysiologic impact of various immune cells in AKI, with special emphasis on repair. An improved understanding of the AKI immunopathology will lead to new therapies that prevent AKI, accelerate repair, and prevent the progression of AKI to chronic kidney disease.

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Section: Immune Cells In Aki Repairmentioning

confidence: 99%

Role of Immune Cells in Acute Kidney Injury and Repair

Lee¹,

Noel²,

Sadasivam

et al. 2017

Nephron

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“…In a mouse warm IRI mode, both pre-treatment and post-treatment of mouse anti-thymocyte globulin increased the percentage of DN T cells but had no obvious effect on kidney injury [40]. Recently, Martina et al [41] indicated that DN T cells were an important subset of the resident T-cell population in the mammalian kidney with anti-inflammatory properties and served as the responders to AKI. It might be interesting if we had investigated the proportion of DN T cells before and after CD28sa administration.…”

Section: Discussionmentioning

confidence: 99%

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Liang

Kuang

et al. 2017

Am J Nephrol

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Background: Regulatory T (Treg) cells are a highly suppressive subset of CD4⁺ lymphocytes and have recently been proved to be crucial to suppress the inflammatory responses of ischemic kidney injury. CD28 superagonists (CD28sa) are monoclonal antibodies that preferentially expand Treg cells without a T-cell receptor and a costimulatory signal. This study aims to test the protection and discover the mechanisms of CD28sa treatment against renal ischemia-reperfusion (IR) injury (IRI). Methods: Male C57BL/6N mice were treated with CD28sa via peritoneal injection (0.1 mg) 6 days before the induction of IRI, or with 18-min ischemic precondition (IPC). IRI was induced by bilateral clamping of renal pedicles for 35 min followed by reperfusion. The role of Treg expansion in renal protection conferred by CD28sa treatment was examined using anti-CD25 antibody. Results: CD28sa treatment alone significantly increased the percentage of Treg cells in the spleen (18.10 ± 2.00 vs. 6.64 ± 0.86%, p < 0.01), peripheral blood (16.43 ± 5.94 vs. 2.57 ± 1.09%, p < 0.01), and kidney (2.69 ± 0.90 vs. 0.53 ± 0.14%, p < 0.01) of C57BL/6N mice 6 days after the administration. Mice pretreated with CD28sa or IPC had less renal injury at 24 h after IRI with attenuation of renal tubular damage and lower serum creatinine compared with the mice that underwent renal IRI alone. The number of infiltrating macrophages in the kidney and IFN-γ secreting CD4⁺ T cells in peripheral blood were diminished in the CD28sa-IR group and the IPC-IR group. The renal protection bestowed by CD28sa or IPC was abolished by anti-CD25 antibody administration. Conclusions: Treg expansion induced by CD28sa ameliorated renal IRI.

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“…In addition, other suppressive cells not belonging to the Th lineage include CD3 + CD4 − CD8 − double‐negative T cells, Qa‐1‐restricted CD8 Tregs and CD28 lo CD8 + Tregs . While these additional regulatory T‐cell subsets have not been as well studied as the conventional CD4 + Foxp3 + Tregs that are discussed in this review, there is evidence for their protective involvement in renal disease …”

Section: Subsets Of Suppressive T Cellsmentioning

confidence: 97%

“…[127][128][129] While these additional regulatory T-cell subsets have not been as well studied as the conventional CD4 + Foxp3 + Tregs that are discussed in this review, there is evidence for their protective involvement in renal disease. 27,123,[130][131][132]…”

Section: Subsets Of Suppressive T Cellsmentioning

confidence: 99%

Regulatory T cells in renal disease

et al. 2018

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The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen‐specific Tregs in HLA‐mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype. Experimentally, Tregs can protect the kidney from injury in a variety of renal diseases. Mechanisms of Treg recruitment to the kidney include via the chemokine receptors CCR6 and CXCR3 and potentially, at least in innate injury TLR9. The effects of Tregs may be context dependent, with evidence for roles for immunoregulatory roles both for endogenous Tbet‐expressing Tregs and STAT‐3‐expressing Tregs in experimental glomerulonephritis. Most experimental work and some of the ongoing human trials in renal transplantation have focussed on unfractionated thymically derived Tregs (tTregs). However, induced Tregs (iTregs), type 1 regulatory T (Tr1) cells and in particular antigen‐specific Tregs also have therapeutic potential not only in renal transplantation, but also in other kidney diseases.

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

Abstract: ABSTRACT

Cited by 74 publications

References 33 publications

Role of Immune Cells in Acute Kidney Injury and Repair

Role of Immune Cells in Acute Kidney Injury and Repair

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Regulatory T cells in renal disease

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