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Transcriptome sequencing of CD8αα T cells and CD8αβ T cells in liver of dnTGFβRII mice.

ABSTRACT: Transcriptome sequencing of CD8αα T cells and CD8αβ T cells in liver of dnTGFβRII mice.

PROVIDER: PRJNA773737 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16532638_1.fastq.gz	Fastqsanger.gz
	SRR16532638_2.fastq.gz	Fastqsanger.gz
	SRR16532639_1.fastq.gz	Fastqsanger.gz
	SRR16532639_2.fastq.gz	Fastqsanger.gz

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Transcriptome sequencing of CD8αα T cells and CD8αβ T cells in liver of dnTGFβRII mice.

Project description:We characterized the tcr repertoire diversity of CD8αα T cells and CD8αβ T cells in liver microenvironment of in dnTGFβRII mice, a classical Primary Biliary Cirrhosis mouse model .

2022-04-22 | GSE186399 | GEO

Gene expression profile of regenerated CD8αα T cells and CD8αβ T cells from LMP2 T-iPSCs

Project description:Whereas cytotoxic T lymphocytes (CTLs) represent the most promising therapeutic avenue in cancer immunotherapy, adaptive transfer of antigen-specific CTLs has faced difficulty in efficient expansion of CTLs from patients in ex vivo culture. To solve this issue, several groups have proposed that the induced pluripotent stem cell (iPSC) technology can be applied for the expansion of antigen-specific CTLs: when iPSCs are produced from antigen-specific CTLs and CTLs are induced from these iPSCs, all regenerated CTLs express the same TCR as original CTLs. However, in these previous studies, one critical issue remains to be solved. With current methods, the regenerated CTLs are mostly of the CD8αα+ innate type and have less antigen-specific cytotoxic activity than primary CTLs. Here we report that, by stimulating purified iPSC-derived CD4/CD8 double positive (DP) cells with anti-CD3 antibody, T cells expressing CD8αβ were generated and they had cytotoxic activity comparable to primary CTLs.

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Gene expression signatures for CD8αβ+ intraepithelial lymphocytes and CD8αβ+ splenocytes.

Project description:CD8αβ+ intraepithelial lymphocytes (IELs) are a subset of “effector-memory-like” T cells scattered along the intestinal epithelium. To investigate if CD8αβ+ IEL can function in ways other than the conventional cytotoxic effect of CD8αβ+ T cells,CD8αβ+ IELs were compared with CD8αβ+ splenocytes (SPL) by RNA-seq. We used microarrays to identify new functions of CD8αβ+ IELs .

2018-05-30 | GSE105061 | GEO

Gene expression signatures for CD8αβ+ intraepithelial lymphocytes and CD8αβ+ splenocytes.

Project description:Gene expression signatures for CD8αβ+ intraepithelial lymphocytes and CD8αβ+ splenocytes.

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BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

Project description:TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs), a specialized subset of T cells in the gut epithelium, develop from thymic agonist-selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in nearly the absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs but the majority thymic PD1+ IELps post agonist selection; its deficiency blocked early IELp generation in the thymus. Moreover, BCL6 expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double positive (DP) thymocytes exhibited increased apoptosis during agonist selection, and impaired IELp differentiation and maturation. Taken together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs.

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Kdm6b is required for the maturation and function of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes

Project description:To under the role of Kdm6b in the regulation of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes (IELs), Kdm6b was conditionally deleted in mouse T cells. Small intestinal TCRβ+CD8αα+ IELs were sorted by flow cytometry and RNA-seq was conducted to identify the differentially expressed genes.

2022-08-02 | GSE154444 | GEO

Intestinal CD4-CD8αβ-TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice

Project description:Intestinal CD4-CD8αβ-TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice

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Generation of TCR-negative CD8αβ+ CAR T cells from T cell-derived induced pluripotent stem cells

Project description:The production of autologous T cells expressing a chimaeric antigen receptor (CAR) is time-consuming, costly and occasionally unsuccessful. T cell-derived induced pluripotent stem cells are a promising source for the generation of ‘off-the-shelf’ CAR T cells, but their in vitro differentiation often yields T cells with suboptimal features. Here we show that premature expression of the T cell receptor (TCR) or a constitutively expressed CAR promote the acquisition of an innate phenotype, which can be averted by disabling the TCR and relying on the CAR to drive T cell differentiation. Delaying CAR expression and calibrating its signalling strength enabled the generation of human CD8αβ+ TCR– CAR+ T cells that perform overall similarly to peripheral blood CD8αβ+ CAR+ T cells in achieving effective tumour control upon systemic administration in a mouse model of leukaemia, without causing graft-versus-host disease. Driving T cell maturation in the absence of a TCR by taking advantage of a CAR may facilitate the large-scale development of potent allogeneic CD8αβ+ T cells for a broad range of immunotherapies. TRAC-1XX-iT cell generation: TiPS were differentiated to the DP T cell stage, and matured to CD8ab SP cells on 3T3-CD19-41BBL. CD8ab SP cells were purified by flow cytometry. Peripheral Blood Mononuclear cells were purified from healthy donor whole blood. CD4 and CD8 T cells were targeted with CD19-28z-1XX CAR into the TRAC locus, NK and gdT cells were retrovirally transduced to express the CD19-28z-1XX CAR. Cells were purified for CAR expression by flow cytometry.

2022-08-23 | GSE210364 | GEO

Intestinal CD4-CD8αβ-TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice

Project description:To distinguish harmless from harmful antigens (Ag), anatomic, cellular and molecular mechanisms operate in the intestinal tract to acquire, process, present and interpret luminal Ags. The intestinal mucosa is populated by many T cell types in the intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) populations, including double negative CD4-CD8αβ-TCRαβ+ T (double-negative T/DNT) cells. Here we show that murine DNT cells in the small intestine reach across the epithelial barrier to capture luminal Ags. A sizeable fraction of DNT cells in Peyer’s patches and mesenteric lymph nodes express MHC-II, but little or no classical co-stimulatory molecules. Indeed, DNT cells acquire, process and present antigenic proteins to tolerize Ag-specific CD4+ T cells. Conditional genetic ablation of MHC-II in T cells disable this tolerogenic function and rendered mutant mice hypersusceptible to intestinal inflammation. Intriguingly, intestinal T cells in patients with Crohn’s disease express lower levels of HLA-DR than those from controls. Our findings thus suggest that MHC-II+ DNT cells may regulate intestinal immune homeostasis and their dysfunction may contribute to the pathogenesis of inflammatory bowel disease.

2025-07-09 | GSE298133 | GEO

CD8αα+MHC-II+ Cell with Capacity to Terminate Autoimmune Inflammation Is A Novel Antigen-Presenting NK-like cell in Rats

Project description:Discovery of immune tolerance mechanisms, which inhibit pre-existing autoimmune inflammation, may provide us with new strategies for treating autoimmune diseases. We have identified a CD8αα+MHC-II+ cell with professional APC capacity during our investigation on spontaneous recovery from autoimmune glomerulonephritis in a rat model. This cell actively invades inflamed target tissue to terminate an on-going autoimmune inflammation by selective killing of effector autoreactive T cells. Now, we showed that this cell used a cytotoxic machinery of Ly49s+ NK cells in killing of target T cells. Thus, this CD8αα+MHC-II+ cell, which previously was thought a professional APC, is an antigen presenting-NK (AP-NK) cell. Following its coupling with target T cells through antigen presentation, killing stimulatory receptor Ly49s6 and co-receptor CD8αα on this cell used non-classic MHC-I RT1CE16 on the target T cells as a ligand to initiate killing. Thus, activated effector T cells with elevated expression of RT1CE16 were highly susceptible to the killing by the CD8αα+ AP-NK cell. Granule cytolytic perforin/granzyme C from this cell subsequently mediated cytotoxicity, and thus, inhibition of granzyme C effectively attenuated the killing. As it can recognize and eliminate effector autoreactive T cells in the inflamed target tissue, CD8αα+ AP-NK cell not only represents a new type of immune cell involved in immune tolerance, but also is a potential candidate for developing a cell-based therapy for pre-existing autoimmune diseases.

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