2019
DOI: 10.3389/fimmu.2019.00883
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Human Double-Negative Regulatory T-Cells Induce a Metabolic and Functional Switch in Effector T-Cells by Suppressing mTOR Activity

Abstract: The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation models, adoptive transfer of DN T-cells specifically inhibits alloreactive T-cells and prevents transplant rejection or graft-vs.-host disease (GvHD). Interestingly, clinical studies in patients who underwent allogeneic stem cell transplantation reveal an inverse correlation between the frequency of circulating DN T-cells and the severity of … Show more

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Cited by 37 publications
(40 citation statements)
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“…Interestingly, there was a significant increase in mean expression of the chemokine receptor CXCR4 on T-cells, B-cells, and mDCs in burn survivors compared to controls (1.67-fold, p < 0.01; 1.81-fold, p < 0.01; and 1.52-fold, p < 0.05, respectively). There was also a significant 0.73-fold decrease (p < 0.05) in the expression of CXCR3 on B-cells and CCR7+ DN T-cells (33,34) in burn survivors, and a trend toward lower Tbet expression in B-cells and higher HLA-DR expression by mDCs.…”
Section: Immunophenotyping By Mass Cytometrymentioning
confidence: 90%
“…Interestingly, there was a significant increase in mean expression of the chemokine receptor CXCR4 on T-cells, B-cells, and mDCs in burn survivors compared to controls (1.67-fold, p < 0.01; 1.81-fold, p < 0.01; and 1.52-fold, p < 0.05, respectively). There was also a significant 0.73-fold decrease (p < 0.05) in the expression of CXCR3 on B-cells and CCR7+ DN T-cells (33,34) in burn survivors, and a trend toward lower Tbet expression in B-cells and higher HLA-DR expression by mDCs.…”
Section: Immunophenotyping By Mass Cytometrymentioning
confidence: 90%
“…We identified another cluster as type 2 innate lymphoid cells (ILC2) based on high expression of the transcription factors Gata3 , Rora, Thy1 , as well as Il7r , Il5, and Il13 coupled with very low levels of Cd3d/e/g , Eomes, Rorc , Tbx21, and Cd4 ( Figures 1 C, 1D, and S2 and Tables S2 and S3 ). This group was also negative for natural killer (NK) and NK T cell markers, e.g., Klra7, Klra8, and Klrb1 ( Haug et al, 2019 ; Juvet and Zhang, 2012 ; Dutton et al, 2018 ; Vivier et al, 2018 ) ( Figure S2 ). An NK cluster with increased relative expression of NK markers, e.g., Gzma, Klra8, Klra7, Klrb1c (NK1.1), Eomes, Ncr1 was identified ( Figures 1 C, 1D, and S2 and Tables S2 and S3 ).…”
Section: Resultsmentioning
confidence: 99%
“…Considering that both the Tregs and the DN T cells compose 1–5% of all T-cells in healthy mice and human subjects [ 24 , 25 ], the shifts in the percentage of Tregs and DN Ts are significant. The LTA-stimulated ARPCs induced a mean Treg decrease from 5.39 cell % of the basal condition to 2.92% in the co-culture at 5 days and from 6.8 to 4.5 cell % at 15 days (Fold changes of 0.55 and 0.67, respectively).…”
Section: Discussionmentioning
confidence: 99%
“…DN Tregs are also antigen-specific suppressor cells. Specifically, they use trogocytosis to regulate T cells with the same antigen specificity and this is a unique feature that makes them appealing for a possible cellular therapy, for transplantation, and for autoimmunity [ 24 , 28 , 31 ]. Recently, the massive presence of this unconventional subset of T cells in normal and ischemic kidneys has been observed both in humans and in mice [ 32 ].…”
Section: Discussionmentioning
confidence: 99%