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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [GFP_HI_LO_scRNASeq]

ABSTRACT: Define genes differentially expressed by Nur77-GFP HI and LO CD4 T cells FACS sorted from the lungs of Mycobacterium tuberculosis-infected mice

ORGANISM(S): Mus musculus

PROVIDER: GSE235799 | GEO | 2023/11/06

REPOSITORIES: GEO

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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [GFP_HI_LO_BULKRNASeq]

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Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.

Project description:After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFPHI cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFPLO cells. By contrast, Nur77-GFPLO cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40+ cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover, OX40 agonist immunotherapy decreases the lung bacterial burden and extends host survival, offering an additive benefit to antibiotics. CD4 T cells from the cerebrospinal fluid of humans with HIV-associated tuberculous meningitis commonly express surface OX40 protein, while CD8 T cells do not. Our data thus propose OX40 as a marker of recently activated CD4 T cells at the infection site and a potential target for immunotherapy in tuberculosis.

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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy

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

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Activated CD4 T cells in tuberculosis express OX40, a target for host-directed immunotherapy [Human_CSF_T_cell_scRNASeq]

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