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

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

PROVIDER: PRJNA708208 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13911650_1.fastq.gz	Fastqsanger.gz
	SRR13911650_2.fastq.gz	Fastqsanger.gz
	SRR13911651_1.fastq.gz	Fastqsanger.gz
	SRR13911651_2.fastq.gz	Fastqsanger.gz
	SRR13911652_1.fastq.gz	Fastqsanger.gz

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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

Transcriptional profiling of human KIR+ CD8 T cells

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

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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.

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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.

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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.

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Regulatory KIR+RA+ T cells accumulate with age and are highly activated during viral respiratory disease

Project description:Severe respiratory viral infectious diseases such as influenza and COVID- 19 espe-cially affect the older population. This is partly ascribed to diminished CD8+ T- cell re-sponses a result of aging. The phenotypical diversity of the CD8+ T- cell population has made it difficult to identify the impact of aging on CD8+ T- cell subsets associated with diminished CD8+ T- cell responses. Here we identify a novel human CD8+ T- cell subset characterized by expression of Killer- cell Immunoglobulin-l ike Receptors (KIR+) and CD45RA (RA+). These KIR+RA+ T cells accumulated with age in the blood of healthy individuals (20– 82 years of age, n = 50), expressed high levels of aging- related mark-ers of T- cell regulation, and were functionally capable of suppressing proliferation of other CD8+ T cells. Moreover, KIR+RA+ T cells were a major T- cell subset becoming activated in older adults suffering from an acute respiratory viral infection (n = 36), including coronavirus and influenza virus infection. In addition, older adults with influ-enza A infection showed that higher activation status of their KIR+RA+ T cells associ-ated with longer duration of respiratory symptoms. Together, our data indicate that KIR+RA+ T cells are a unique human T- cell subset with regulatory properties that may explain susceptibility to viral respiratory disease at old age.

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

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

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Transcriptional profiling of human KIR+ CD8 T cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-08 | GSE193442 | GEO