A new chapter in the CD8 T reg story

Cantor, Harvey; Kim, Hye-Jung

doi:10.1084/jem.20201746

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…Further, the abovementioned functions of TGF-b and Eomes are CD8 + T cell-specific without impacting CD4 + T cells including CD4 + Tregs. Thus, our findings may establish DKO mice as a valuable CD8 + Treg deficient model with an intact CD4 + Treg compartment (50). Strikingly, our results also reveal that CD8 + Tregs are extremely potent suppressors of autoimmunity (20).…”

Section: Cd122 Hi Ly49 + Cd8 + Treg -Discovery and Functionsupporting

confidence: 58%

CD8+ Regulatory T Cell – A Mystery to Be Revealed

Mishra

Srinivasan

et al. 2021

Front. Immunol.

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Regulatory T cells (Treg) are essential to maintain immune homeostasis and prevent autoimmune disorders. While the function and molecular regulation of Foxp3+CD4+ Tregs are well established, much of CD8+ Treg biology remains to be revealed. Here, we will review the heterogenous subsets of CD8+ T cells have been named “CD8+ Treg” and mainly focus on CD122hiLy49+CD8+ Tregs present in naïve mice. CD122hiLy49+CD8+ Tregs, which depends on transcription factor Helios and homeostatic cytokine IL-15, have been established as a non-redundant regulator of germinal center (GC) reaction. Recently, we have demonstrated that TGF-β (Transforming growth factor-β) and transcription factor Eomes (Eomesodermin) are essential for the function and homeostasis of CD8+ Tregs. In addition, we will discuss several open questions regarding the differentiation, function and true identity of CD8+ Tregs as well as a brief comparison between two regulatory T cell subsets critical to control GC reaction, namely CD4+ TFR (follicular regulatory T cells) and CD8+ Tregs.

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Section: Cd122 Hi Ly49 + Cd8 + Treg -Discovery and Functionsupporting

confidence: 58%

CD8+ Regulatory T Cell – A Mystery to Be Revealed

Mishra

Srinivasan

et al. 2021

Front. Immunol.

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“…Importantly, these KIR + CD8 + cells are shown to suppress autoreactivity by direct killing of pathogenic CD4 T cells 39 . Functionally and phenotypically similar cells were described earlier in mice as CD8 + Treg cells [40][41][42] . Here, the uIELs were found to be able to kill target cells ex vivo.…”

Section: Discussionsupporting

confidence: 69%

Single-cell profiling identifies a spectrum of human unconventional intraepithelial T lineage cells

Billiet

Cock

Sanchez

et al. 2022

Preprint

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In the human thymus, a CD10+ PD-1+ TCRαβ+ differentiation pathway diverges from the conventional single positive T cell lineages at the early double positive stage. These cells are phenotypically and functionally similar to murine unconventional intraepithelial lymphocyte (uIEL) precursors. Here, the progeny of the human uIEL lineage was identified in antigen-inexperienced blood. The uIELs in thymus and peripheral blood share a transcriptomic profile, characterized by hallmark transcription factors (i.e. ZNF683 and IKZF2), and polyclonal TCR repertoire with autoreactive features, exhibiting a bias towards early TCR alpha chain rearrangements. Single-cell RNA sequencing confirmed a common developmental trajectory between the thymic and peripheral uIELs, and clearly delineated this unconventional lineage in peripheral blood. This population is phenotypically defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. It contains CD10+ recent thymic emigrants, Helios+ KIR+ CD8+ Tregs and CD8αα+ T cells. Thus, the uIEL lineage represents a well-defined but heterogeneous, unconventional TCRαβ+ lineage mostly confined in human within the CD8 single positive T cells.

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Double-negative T cells have a reparative role after experimental severe ischemic acute kidney injury

Lee,

Gharaie,

Kurzhagen

et al. 2024

American Journal of Physiology-Renal Physiology

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T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR+ CD4- CD8-), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental AKI. However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared to gold-standard anti-inflammatory CD4+ Tregs. In vitro effects of DN T cells and Tregs on renal tubular epithelial cell (RTEC) repair after injury were quantified with live-cell analysis. DN T cells, Tregs, CD4 or vehicle were adoptively transferred after severe AKI. Glomerular filtration rate (GFR) was measured using FITC-sinistrin. Fibrosis was assessed with Masson's trichrome staining. Profibrotic genes were measured with qRT-PCR. Percentages and the numbers of DN T cells substantially decreased during repair phase after severe AKI, as well as their activation and proliferation. Both DN T cells and Tregs accelerated RTEC cell repair in vitro. Post-AKI transfer of DN T cells reduced kidney fibrosis and improved GFR, as did Treg transfer. DN T cell transfer lowered TGFβ1 and αSMA expression. DN T cells reduced effector-memory CD4+ T cells and IL-17 expression. DN T cells undergo quantitative and phenotypical changes after severe AKI, accelerate RTEC repair in vitro as well as improve GFR and renal fibrosis in vivo. DN T cells have potential as immunotherapy to accelerate repair after AKI.

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A new chapter in the CD8 T reg story

Cited by 3 publications

References 16 publications

CD8+ Regulatory T Cell – A Mystery to Be Revealed

CD8+ Regulatory T Cell – A Mystery to Be Revealed

Single-cell profiling identifies a spectrum of human unconventional intraepithelial T lineage cells

Double-negative T cells have a reparative role after experimental severe ischemic acute kidney injury

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