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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

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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 (4)

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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

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

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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.

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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

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Project description:The development of CD4+ T cells and CD8+ T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-MHCI or MHCII by the T cell antigen receptor (TCR) determines the CD8+ T cell or CD4+ T cell lineage choice, respectively, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. Here we applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and T cell lineage-restricted mice to generate a comprehensive timeline of cell state for each T cell lineage. These analyses identified a sequential process whereby all thymocytes initiate CD4+ T cell lineage differentiation during an initial wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8+ T cell lineage specification. CITE-seq and pharmaceutical inhibition experiments implicated a TCR-calcineurin-NFAT-GATA3 axis in driving the CD4+ T cell fate. Our data provide a resource for understanding cell fate decisions and implicate multiple redundant mechanisms in guiding lineage choice.

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