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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (5)

ABSTRACT: Here we report bulk TCR sequencing data associated with open repertoire murine CD4+, CD4+CD8+, and CD8+ T cells isolated from B16 melanoma tumor resections

ORGANISM(S): Mus musculus

PROVIDER: GSE203187 | GEO | 2022/05/20

REPOSITORIES: GEO

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (3)

Project description:Here we report transcriptional and TCR specificities associated with murine open repertoire CD45.1+ CD4+ and CD4+CD8+, and CD45.2+ CD8+ and CD8+CD4+ T cells isolated from murine B16 tumors

2022-05-20 | GSE203184 | GEO

Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (1)

Project description:Here we report transcriptional specificities associated with murine Trp1 CD4+ and Trp1 CD4+CD8+ T cells isolated from B16 melanoma tumor resections.

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (6)

Project description:Here we report ATAC sequencing data from sorted antigen specific Trp1 CD4+ and CD4+CD8+, and Pmel CD8+ and CD8+CD4+ T cells in steady state (naïve, no tumor) mice and also in B16-tumor bearing animals

2022-05-20 | GSE203188 | GEO

Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (4)

Project description:Here we report RNA sequencing data from sorted antigen specific Trp1 CD4+ and CD4+CD8+, and Pmel CD8+ and CD8+CD4+ T cells in steady state (naïve, no tumor) mice and also in B16-tumor bearing animals

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Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (2)

Project description:Here we report transcriptional and TCR specificities associated with melanoma patient TIL populations.

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Lupus milieu favors the conversion of self-reactive CD8 T cells to IL-17 producing double negative T cells

Project description:Mature double negative (DN) T cells are αβ T cells lacking CD4/CD8 coreceptors and expanded in patients with systemic lupus erythematosus (SLE). It is not known whether they display a narrow or expander TCR repertoire.

2020-04-24 | GSE149239 | GEO

Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions.

Project description:Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics.

| S-EPMC9130031 | biostudies-literature

TCR repertoire analysis revealed the mobilization of novel CD8+ T cell clones into Cancer-Immunity Cycle following anti-CD4 antibody administration

Project description:Depletion of CD4+ cells by anti-CD4 monoclonal antibody (anti-CD4 mAb) induces expansion of tumor-reactive CD8+ T cells and exhibits strong antitumor effects in several murine tumor models. However, whether the anti-CD4 mAb treatment activates particular or a broad variety of tumor-reactive CD8+ T cell clones is not answered. To investigate the changes of TCR repertoire induced by the anti-CD4 mAb treatment, we performed unbiased high throughput TCR sequencing in a B16F10 mouse subcutaneous melanoma model.

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scRNA-seq of mouse thymocyte CD4 CD8 lineage choice and differentiation

Project description:CD4 and CD8 identify helper and cytotoxic T cell lineages, and serve as co-receptors for MHC-restricted TCR recognition. Despite decades of investigation, questions remain about how TCR specificity and co-receptor gene expression are matched during T cell repertoire selection. Here we address the order and logic of CD4/CD8 lineage choice and differentiation by scRNA-seq. Maturation, activation, and lineage specification emerged as principle components, in this order. Co-receptor gene expression uncovered waves of Cd4+Cd8a+, Cd4+Cd8a- and Cd4-Cd8a+ selection intermediates and revealed gene expression programs associated with each pattern, including TCR- and cytokine signaling genes, lineage markers and transcription factors. While in the unperturbed thymus early Cd4+Cd8a+ selection intermediates were followed first by CD4-like Cd4+Cd8a- and later by CD8-like Cd4-Cd8a+ selection intermediates, the order of co-receptor gene expression was not inherently fixed. These data provide a benchmark for models of CD4/CD8 lineage choice, and a rich resource for interrogating T cell differentiation.

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Anti-CD4 treatment affects TCR repertoire of CD8+ T cells

Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, elicits robust anti-tumor immunity in various cancers by increasing tumor-infiltrating lymphocytes and promoting CD8+ T cell reactivity against tumor cell-derived antigens. We conducted TCR repertoire analysis of anti-CD4-exposed endogenous CD8+ T cells to investigate the expansion pattern of the cell population.

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