Cytomegalovirus-Associated CD4+CD28null Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction

Shabir, Shazia; Smith, Helen; Kaul, Baksho; Pachnio, Annette; Jham, Seema; Kuravi, Sahithi J.; Ball, Simon; Chand, Sourabh; Moss, Paul; Harper, Lorraine; Borrows, Richard

doi:10.1111/ajt.13614

Cited by 31 publications

(36 citation statements)

References 34 publications

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“…B), indicating that these cells exhibit potential to migrate into the intestine. Several studies show that CD4 + NKG2D + T cells with CD28 negative expression have autoreactivity and promote local inflammation . In the present study, NK1.1 − CD4 + NKG2D + T cells increased CD28 expression level compared with NK1.1 − CD4 + NKG2D − T cells in both DSS‐treated and control mice.…”

Section: Resultssupporting

confidence: 58%

NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Qian

Han

et al. 2017

J Cellular Molecular Medi

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CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN‐γ and TNF‐α to promote inflammation, but others produce TGF‐β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1− CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1− CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS‐induced colitis. NK1.1− CD4+ NKG2D+ cells expressed TGF‐β and FasL without secreting IFN‐γ, IL‐21 and IL‐17 and displayed no cytotoxicity. The adoptive transfer of NK1.1− CD4+ NKG2D+ cells suppressed DSS‐induced colitis largely dependent on TGF‐β. NK1.1− CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG‐3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1− CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA‐3 and ROR‐γt. Thus, NK1.1− CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

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Section: Resultssupporting

confidence: 58%

NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Qian

Han

et al. 2017

J Cellular Molecular Medi

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“…Shabir et al followed an unselected group of kidney transplant recipients and examined the CD28− CD4 T cells. These cells were found predominantly in CMV-seropositive patients and expanded posttransplantation; they had an effector memory phenotype and expressed CX3CR1 as well as NKG2D and perforin (132). …”

Section: Infections In Which Cd4 Ctl Are Protectivementioning

confidence: 99%

Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

et al. 2017

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CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections.

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“…It should be noted that the loss of CD28 on CD4 T cells has been implicated in promoting immunosuppression resistance and allograft rejection (6970) due to the cytotoxic capacity of these cells. Very recently it was reported that increases in circulating CD4 + CD28 − CD57 + T cells prior to transplantation is associated with belatacept resistant rejection (BRR) post-transplantation (7172). Furthermore, cytomegalovirus-related, cytotoxic CD4 + CD28 − T cells potentiate kidney allograft dysfunction by glomerular endothelial injury in an NKG2D-dependent manner.…”

Section: Clinical Relevance Of Cd4+cd28− T Cellsmentioning

confidence: 99%

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

Lee

2016

Immune Netw

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CD28 is a primary co-stimulatory receptor that is essential for successful T cell activation, proliferation, and survival. While ubiquitously expressed on naive T cells, the level of CD28 expression on memory T cells is largely dependent on the T-cell differentiation stage in humans. Expansion of circulating T cells lacking CD28 was originally considered a hallmark of age-associated immunological changes in humans, with a progressive loss of CD28 following replicative senescence with advancing age. However, an increasing body of evidence has revealed that there is a significant age-inappropriate expansion of CD4+CD28− T cells in patients with a variety of chronic inflammatory diseases, suggesting that these cells play a role in their pathogenesis. In fact, expanded CD4+CD28− T cells can produce large amounts of proinflammatory cytokines such as IFN-γ and TNF-α and also have cytotoxic potential, which may cause tissue damage and development of pathogenesis in many inflammatory disorders. Here we review the characteristics of CD4+CD28− T cells as well as the recent advances highlighting the contribution of these cells to several disease conditions.

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Cytomegalovirus-Associated CD4+CD28null Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction

Cited by 31 publications

References 34 publications

NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

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Cytomegalovirus-Associated CD4+CD28null Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction

Cited by 31 publications

References 34 publications

NK1.1−CD4+NKG2D+ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

NK1.1−CD4+NKG2D+ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

Unusual CD4+CD28−T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

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NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders