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KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans

ABSTRACT: KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans

PROVIDER: PRJNA769687 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16249109.fastq.gz	Fastqsanger.gz
	SRR16249110.fastq.gz	Fastqsanger.gz
	SRR16249111.fastq.gz	Fastqsanger.gz
	SRR16249112.fastq.gz	Fastqsanger.gz
	SRR16249113.fastq.gz	Fastqsanger.gz

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KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans

Project description:We studied the heterogeneity among human KIR/NKG2A+CD8+ T cells. First, we found that KIRs and NKG2A are expressed on human CD8+ T cells in a mutually exclusive manner. Therefore, we compared KIR+CD8+ and NKG2A+CD8+ T cells in regards to TCR overlap and transcriptomic profiles and demonstrated that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations.

2023-02-23 | GSE185567 | GEO

Transcriptional profiling of human KIR+ and KIR- CD8 T cells by bulk RNA-seq

Project description:Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalents of the Ly49 family, in the blood and inflamed tissues of various human autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients’ leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and correlate with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.

2022-03-08 | GSE168527 | GEO

Elevation of KIR+CD8+ T cells during human pregnancy

Project description:During pregnancy, immune responses must balance fetal protection from infections with tolerance of the semi-allogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified KIR+CD8+ T cells as a previously underappreciated regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR+CD8+ T cells in the peripheral blood of pregnant women at the second trimester, especially in those carrying a male fetus. In vitro, KIR+CD8+ T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and suppressed HY-specific CD8+ T cells from mothers with a male fetus. Therefore, the higher induction of KIR+CD8+ T cells in mothers carrying a male fetus may help suppress additional allogenic responses triggered by Y chromosome antigens. Longitudinal analysis showed that KIR+CD8+ T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single cell RNA-seq analysis of decidual CD8+ T cells from early pregnancy revealed elevated number and activity of KIR+ CD8+ T cells at the maternal-fetal interface. In addition, increased levels of KIR+CD8+ T cells correlated with pregnancy disorders (e.g., spontaneous abortion and preeclampsia). Taken together, our findings suggest an important role of KIR+CD8+ T cells in the maintenance of maternal tolerance by suppressing fetal-specific alloreactive T cells. They may also be useful as predictive biomarkers or drug targets for human pregnancy disorders.

2025-08-01 | GSE281341 | GEO

Single-cell RNA-seq analysis of human KIR+ CD8 T cells by Smart-seq2

Project description:KIR+ CD8 T cells (Live CD3+CD56-TCRab+CD8+KIR+ cells) were sorted from the blood of healthy subjects (N=10) and patients with MS (N=2), SLE (N=6), or CeD (N=5) and subjected to single-cell RNA-seq analysis by Smart-seq2. In parallel, we also analyzed their T-cell receptor (TCR) α and β sequences. Unsupervised clustering of these KIR+CD8+ T cells by Seurat identified six clusters, with Clusters 1 to 3 mostly containing expanded KIR+CD8+ T cells (≥2 cells expressing same TCR) and Clusters 5 and 6 consisting of unexpanded cells expressing unique TCRs. There are common features shared by KIR+CD8+ T cells from healthy subjects and different diseases, yet there is also heterogeneity (i.e., upregulated type I IFN signaling and glycolysis in Clusters 2 and 3) associated with different diseases or treatments.

2022-03-08 | GSE193439 | GEO

IL-12 drives the expression of the inhibitory receptor NKG2A on human tumor-reactive CD8 T cells

Project description:Blockade of NKG2A/HLA-E interaction is a promising strategy to unleash the anti-tumor response. Yet the regulation of NKG2A expression on CD8+ lymphocytes and the T cell anti-tumor response are still poorly understood. Here, by performing CITE-seq on human T cells derived from head and neck squamous cell carcinoma and colorectal cancer, we show that NKG2A expression is induced in tumor-infiltrating CD8+ T cells differentiating into cytotoxic, CD39+CD103+ double positive (DP) T cells. This developmental trajectory lead to TCR repertoire overlap between the NKG2A– and NKG2A+ DP CD8 T cells, suggesting shared antigen specificities. Mechanistically, IL-12 is essential for the expression of the NKG2A on naïve CD8+ T cells in a CD40/CD40L- dependent manner, in conjunction with TCR stimulation and increased TGF-β levels. Our study thus reveals that NKG2A is induced by IL-12 on human tumor-reactive CD8+ T cells exposed to a TGF-b-rich environment, highlighting an underappreciated immuno-regulatory feedback loop dependent on IL-12 stimulation.

2024-10-08 | GSE278692 | GEO

NKG2A educates uterine NK cells to optimise pregnancy outcomes in humans and mice

Project description:We report abnormal pregnancy outcomes in mice lacking NKG2A, including altered placental transcription. In humans, we find HLAB-21T snp to be associated with an increased risk of pre-eclampsia.

2021-04-29 | GSE173478 | GEO

Transcriptional profiling of human KIR+ CD8 T cells

Project description:Transcriptional profiling of human KIR+ CD8 T cells

| PRJNA796265 | ENA

Transcriptional profiling of human KIR+ and KIR- CD8 T cells by bulk RNA-seq

Project description:Transcriptional profiling of human KIR+ and KIR- CD8 T cells by bulk RNA-seq

| PRJNA708208 | ENA

CD94/NKG2A-Qa-1b Axis as a Key Modulator of Vaccine Responsiveness in Aging Populations

Project description:Vaccine responses decline with age, yet underlying mechanisms remain unclear. Using an Alum-adjuvanted spike (S+Alum) vaccine, this study identifies an aging-linked pathway in which senescence-associated secretory phenotype cytokines (CCL2, IL-6, IFN-γ) at the injection site are upregulated and associate with increased H2-T23 (Qa-1b) expression on monocytes. These H2-T23high monocytes interact with MHCIIhigh cDC2 via IL-10/TGF-β, limiting dendritic-cell antigen presentation, and engage the CD94/NKG2A-Qa-1b checkpoint on T cells, further dampening immunity. In humans, HLA-E+ monocytes and NKG2A⁺ T cells are infrequent in young individuals but show higher prevalence in peripheral blood from older adults, highlighting this pathway as a regulatory target. Blocking the CD94/NKG2A-Qa-1b axis thus emerges as a potential strategy to enhance vaccine performance in aging populations. Overall, the findings define a mechanistic link between SASP-driven myeloid programming, impaired antigen presentation, and checkpoint-mediated T-cell restraint in aging, with implications for vaccine design tailored to older individuals.

2025-09-30 | GSE309190 | GEO

Elevation of KIR+CD8+ T cells during human pregnancy

Project description:Elevation of KIR+CD8+ T cells during human pregnancy

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