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Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE163345 | GEO | 2021/09/20

REPOSITORIES: GEO

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Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [scRNA-seq]

Project description:Inhibiting PD1:PDL1 signaling has transformed therapeutic immune restoration. CD4 T cells are critical to sustain immunity in chronic infections and cancer, yet little is known about how PD1/L1 modulates CD4 T helper (Th) responses or the ability to restore CD4 Th-mediated immunity by inhibiting PD1/L1 signaling. We demonstrate that PD1/L1 specifically suppresses CD4 Th1 cell amplification, prevents CD4 Th1 cytokine production, and abolishes CD4 CTL killing capacity during chronic infection. Inhibiting PDL1 during chronic infection rapidly restored these functions, while simultaneously enhancing Th1-like Treg amplification and activation, indicating a system-wide CD4-Th1 recalibration. Paradoxically, PDL1-blockade decreased TCR signaling, while re-directing intrinsically-suppressive type I interferon networks towards dominant IFNγ-mediated responses. Mechanistically, PDL1-blockade specifically targeted defined populations with pre-established, but actively-suppressed proliferative potential, with limited impact on minimally-cycling TCF1+ Tfh, despite high PD1 expression. Thus, CD4 T cells require unique differentiation and functional states to be targets of PDL1-directed suppression and therapeutic restoration.

2021-09-20 | GSE163343 | GEO

Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [Bulk-seq]

2021-09-20 | GSE163259 | GEO

Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection

Project description:Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection

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Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [Bulk-seq]

Project description:Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [Bulk-seq]

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Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [scRNA-seq]

Project description:Dynamic CD4 T cell heterogeneity defines subset-specific suppression and PDL1-blockade driven functional restoration in chronic infection [scRNA-seq]

| PRJNA685782 | ENA

Olfactomedin 4 defines a subset of human neutrophils.

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CSF1/CSF1R Axis Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1 Immunotherapy.

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Integrin alpha-6 (CD49f) defines a novel and distinct subset of CD4+ regulatory T cells with potent suppression activity.

Project description:A common method used both in vitro and in vivo, to identify Tregs in CD4+ T cells is through the characterization of surface marker CD25. Although CD25 expression is well correlated with regulatory activity in vitro, CD4+CD25+ T cells are not the only regulatory CD4+ T cells in vivo. Studies suggest that in many situations, CD4+CD25M-bM-^@M-^S T cells are as effective as CD4+CD25+ T cells in controlling T cell mediated disease. Therefore, CD25 is not a uniquely specific cell surface marker for the identification of Tregs. CD49f is an M-NM-16-integrin subunit which dimerizes with either the M-NM-2 1 or M-NM-2 4 subunit to form receptors for various laminin isoforms. We found that CD4+ T cells from NOD mice express CD49f, and old non-diabetic NOD mice had an increase of CD4+CD49f+ T cells in the spleen and peripheral lymph node when compared to both young and diabetic mice. This study was conducted to further characterize CD4+CD49f+ Treg cell subpopulation in NOD mice. It was found that CD4+CD49f+T cells possess suppressive ability and only one third of CD4+CD49f+ T cells expressing CD25. Based on the expression of CD49f and CD25, CD4+ T cells was divided into four populations , CD25+CD49f+ ,CD25+CD49f- ,CD25-CD49f+ but CD25-CD49f- are of suppressive ability, and we further found that Foxp3 expression was highly correlated with the suppressive ability of these three Treg populations. In conclusion our data indicate that CD49f marks a CD4+ CD25+ Treg subset with more potent suppression activity and identifies a CD25-CD4+ T cell population with suppression function in a Foxp3+ expression dependent manner. We divided CD4+ T cells into four populations: CD25+CD49f+, CD25+CD49f-, CD25-CD49f+, CD25-CD49f-; Microarray technology was used to determine gene expression differences among these four groups.

2012-05-09 | E-GEOD-30503 | biostudies-arrayexpress

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