Bulk RNA-sequencing of CD7+ and CD7- CD8 T cells from chronic LCMV infection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE284025 | GEO | 2025/09/11
REPOSITORIES: GEO
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Project description:Bulk RNA-sequencing of CD7+ and CD7- CD8 T cells from chronic LCMV infection
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Project description:Chronic viral infections are characterized by a state of CD8 T cell dysfunction termed exhaustion. A better understanding of the mechanisms that regulate CD8 T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8 T cells. Here we identify a novel population of virus-specific CD8 T cells with a T follicular helper (Tfh)-like signature in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These Tfh-like CD8 T cells expressed the programmed cell death-1 (PD-1) inhibitory receptor but at the same time also expressed co-stimulatory molecules and had a gene signature that was related to CD8 T cell memory precursor cells and hematopoietic stem cells (HSC). These Tfh-like CD8 T cells acted as stem cells during chronic infection undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells that were present in both lymphoid and non-lymphoid tissues. The Tfh-like CD8 T cells were found only in lymphoid tissues and resided predominantly in the T cell zones along with naïve CD8 T cells. Interestingly, the proliferative burst after PD-1 blockade came almost exclusively from this Tfh-like CD8 T cell subset. Importantly, the transcription factor TCF1 played a cell intrinsic and essential role in the generation of Tfh-like CD8 T cells. Taken together, our study identifies Tfh-like CD8 T cells as the critical subset for maintaining the pool of virus-specific CD8 T cells during chronic infection and as the cells that proliferate after PD-1 blockade. These findings provide a better understanding of T cell exhaustion and have implications towards optimizing PD-1 directed immunotherapy. 8 samples isolated from CD8 T-cells in LCMV clone 13 GK1.5 infected mice (2 naïve, 3 CXCR5+Tim3-, 3 CXCR5-Tim3+) cells were analyzed
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Project description:Chronic viral infection results in CD8 T cell exhaustion. Here, we use paired single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) to investigate CD8 T cell phenotypic and clonal heterogeneity in multiple mice during the late stage of LCMV Clone 13 infection.
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Project description:T cells specific for a certain antigen are a heterogeneous population characterized by cells expressing different T Cell Receptors (TCRs). As the TCR determines the avidity of a T cell clone for its cognate antigen, this feature has also a significant impact on the fate of such clone during antigenic challenge. In the context of chronic viral infection, T cells specific for the chronic virus differentiate into exhausted cells with limited functionality. We find that, in the process of exhaustion following infection with LCMV-Clone13, certain clones of CD8 T cells specific for the LCMV immunodominant epitope GP33 are enriched compared to others.
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