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The in vitro expanded CD8+ T cells and its controls

ABSTRACT: CD8+ NKT cells are naturally occurring but rare T cells that express both T cell and natural killer (NK) cell markers. These cells may play key roles in establishing tolerance to self antigens; however, the mechanism of action and the molecular profiles of these cells are poorly characterized due to their extremely low frequencies. We developed a highly efficient in vitro conversion/expansion protocol for such cells and extensively characterized their functional and molecular phenotypes using a variety of genomic and immunological techniques. We used microarrays to elucidate the molecular mechanisms underlying the suppression function of the converted CD8+ NKT cells. Keywords: Cell type comparison

ORGANISM(S): Mus musculus

PROVIDER: GSE10813 | GEO | 2009/02/01

SECONDARY ACCESSION(S): PRJNA107407

REPOSITORIES: GEO

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The in vitro expanded CD8+ T cells and its controls

Project description:CD8+ NKT cells are naturally occurring but rare T cells that express both T cell and natural killer (NK) cell markers. These cells may play key roles in establishing tolerance to self antigens; however, the mechanism of action and the molecular profiles of these cells are poorly characterized due to their extremely low frequencies. We developed a highly efficient in vitro conversion/expansion protocol for such cells and extensively characterized their functional and molecular phenotypes using a variety of genomic and immunological techniques. We used microarrays to elucidate the molecular mechanisms underlying the suppression function of the converted CD8+ NKT cells. Keywords: Cell type comparison To identify candidate genes that might be related to the suppressive activity, the CD8+ NKT cells with potent suppressive activity were compared to three different control cells: 1) CD4+ T cells (with very weak suppression) cultured under the same condition as a control for culture condition, 2) naïve CD8 T cells as the baseline expression level, and 3) CD8+ T cells activated using conventional activation protocols. The last two cell populations do not possess suppressive activity. This data set allows us to examine a number of different questions

2009-02-01 | E-GEOD-10813 | biostudies-arrayexpress

RNAseq analysis of mature thymic NKT cells and immature thymic DN1eP cells

Project description:We report the identification of immature thymic CD4(-),CD8(-) double-negative (DN)1e cells with the NKT cell lineage potential. We also analyzed the gene expression profiles of DN1e thymocytes compared with those of mature thymic NKT cell developmental stages termed NKT stage-1, 2, and -3, which are characterized by differential expression levels of NK1.1 and CD44 antigens in C57BL/6 mouse strain. Next generation sequencing of total transcriptomes using total RNA isolated from FACS sorted ex vivo thymic DN1eP (Lin-/CD44+/CD25-/CD24low/CD5+/CD27+/Ly108-/CXCR3+) fraction, and mature thymic alphaGalCer-loaded CD1d dimer+TCRbeta+ NKT cell developmental stage-1 (CD44-/NK1.1-), stage-2 (CD44+/NK1.1-), and stage-3 (CD44+/NK1.1+) cells.

2015-12-31 | E-GEOD-53150 | biostudies-arrayexpress

RNAseq analysis of mature thymic NKT cells and immature thymic DN1eP cells

2015-12-31 | GSE53150 | GEO

A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

Project description:Transcriptome sequencing of sorted CD127+ DN T cells, MAIT, NKT, and CD127+CD4 and Cbir DN to identify transcriptional signatures of CD4 and CD8 double negative T cells.

2022-11-03 | E-MTAB-11397 | biostudies-arrayexpress

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [CSF]

Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TEMRA]

2019-11-04 | GSE134576 | GEO

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TCR-seq]

2019-11-04 | GSE135051 | GEO

A comparison of the transcriptional profiles of DP CD24highCD44lowNK1.1-CD1d-tet+TCRa+ cells (i.e. very immature NKT cells) with those of more mature NKT cell subsets

Project description:Type 1 NKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their functional characteristics are distinct from conventional T cells, and are induced by a transcriptional program initiated by positive selection on CD4+CD8+ (double positive, DP) thymocytes. Here we examined transcriptional events in four immature thymic NKT cell subsets in a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24+CD44- NKT cells. We used a transcriptional regulatory network approach to map TCR validation to the transition from DP T to DP NKT cells, and positive selection and lineage commitment to the transition from DP NKT to CD4 NKT

2021-12-15 | GSE106720 | GEO

Role of TCR:peptide/MHC Class I Affinity in Directing Different Maturation Phenotypes of Dominant and Subdominant Epitope-Specific CD8+ T Cells in Mamu-A*01+ Rhesus Monkeys

Project description:CD8+ T cells that bind different regions of proteins derived from a virus are often present at different frequencies. It is thought that those virus-specific CD8+ T cells that are present at the highest frequency are predominantly responsible for control of viral infections. While the number of virus-specific CD8+ T cells is undoubtedly important, the functionality of these cells may also play a role in their anti-viral capacity. It was not known if virus-specific CD8+ T cells present at high frequencies are more functionally effective against viral infection than those present at low frequencies. In this study, we characterized the functional differences between the SIV-specific cells present at high frequencies to those present at low frequencies in the blood of rhesus monkeys infected with simian immunodeficiency virus (SIV). We found that the high-and low-frequency SIV-specific cells had different functional capacities both during acute and chronic SIV infection. We also found that the strength with which a cell interacts with the proteins derived from the virus may contribute to the functional differences between the high- and low-frequency cells. These findings further our understanding of anti-viral responses and may inform HIV vaccine design.

2014-04-24 | GSE54001 | GEO

Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis

Project description:Immune checkpoint inhibitor (ICI) therapies have improved outcomes for advanced malignancies by activating T cell responses, yet often also elicit harmful autoimmune reactions. The T cell mechanisms mediating these iatrogenic autoimmune events remain unclear. Here we focused on ICI-induced inflammatory arthritis (ICI-arthritis), which can clinically present indistinguishable from rheumatoid arthritis (RA). Compared to autoimmune RA and psoriatic arthritis (PsA), we found ICI-arthritis joints contained an expanded CD38hiCD127- CD8 T cell subset that displays cytotoxic, effector, and interferon (IFN) response signatures. Synovial T cells exposed to Type I IFN, more so than IFN-γ, induced the CD38hi cytotoxic phenotype. Single cell transcriptomic and T cell repertoire (TCR) analyses indicated the abundant CD38hi CD8 T cells resulted from local proliferation of a limited number of clones. The CD38hi phenotype was distinct from dysfunctional T cells and clonally most related to a TCF7+ memory population. Comparing CD8 T cells from both knees in a patient demonstrated considerable sharing of the CD38hi expanded TCR clonotypes. Further, expanded TCR clonotypes from the joints were detected in the circulation, and together with higher frequencies of circulating CD38hi CD8 T cells, represent potential biomarkers for irAEs. These results define a distinct CD8 T cell subset in humans that is activated by ICI therapy and mediates tissue-specific autoimmunity.

2023-12-31 | GSE205501 | GEO

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