Exhausted-like CD8 resident memory T cells balance immunity and fibrotic sequelae
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115786 | GEO | 2019/03/21
REPOSITORIES: GEO
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Project description:Exhausted-like CD8 resident memory T cells balance immunity and fibrotic sequelae
| PRJNA476002 | ENA
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147263 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147081 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147080 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147021 | GEO
Project description:Tissue-resident memory T (Trm) cells express CD103 to be maintained in the local microenvironment and to be strongly involved in local immunity of epithelial tissue. Trm has been associated with cytotoxicity in pathologies of not only virus infection and autoimmune disease but also many cancers. Tumor infiltration by CD103+ Trm cells was associated with patient survival in colorectal cancer. Tumor infiltrating CD103+ Trm cells were comprised predominantly of CD8 T cells expressing cytotoxic activation and immune check-point molecules called exhausted markers. Therefore, we focused on ZNF683 as a marker of cancer-specific Trm. The expression of ZNF683 in Trm was up-regulated by TCR and IFN-γ signaling that was positive feedback by autocrine IFN-γ. These results indicate that IFN-γ and TCR signaling and ZNF683 are involved in the activation of Trm in tumor and would be promising targets for regulation of cancer immunity.
2022-03-25 | GSE188381 | GEO
Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA
2012-08-29 | E-GEOD-39152 | biostudies-arrayexpress
Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.
2008-06-16 | E-GEOD-9650 | biostudies-arrayexpress
Project description:CD8+ memory T cells are critical components of protective immunity to intracellular pathogens and tumors. While many memory CD8+ T cells recirculate throughout the body, others remain lodged in tissues and guard common sites of pathogen entry. Contributions of the specific tissue environment to tissue-resident memory T cell (Trm) differentiation and homeostasis have been implicated but are not well understood. Here, we define the diversity of gene expression and genome accessibility by mouse CD8+ Trm populations in distinct organs and identify molecules critical for Trm generated in response to acute viral infection. We find that CD8+ TRM across different tissues possess both shared and tissue-specific transcriptional and epigenetic signatures. Notably, Trm in the intestine and salivary gland express TGFb-induced genes and are maintained by ongoing TGFb signaling while those in the fat, kidney, and liver are not. By constructing transcriptional-regulatory networks for each Trm population, we identify the repressor Hic1 as a critical regulator of Trm differentiation, particularly for Trm of the small intestine. This study provides a framework for understanding how Trm adapt to distinct tissue environments and identifies tissue-specific transcriptional regulators that mediate these adaptations, informing strategies to enhance protective memory responses at the sites most vulnerable to infection.
2022-04-18 | GSE182275 | GEO
Project description:CD8+ memory T cells are critical components of protective immunity to intracellular pathogens and tumors. While many memory CD8+ T cells recirculate throughout the body, others remain lodged in tissues and guard common sites of pathogen entry. Contributions of the specific tissue environment to tissue-resident memory T cell (Trm) differentiation and homeostasis have been implicated but are not well understood. Here, we define the diversity of gene expression and genome accessibility by mouse CD8+ Trm populations in distinct organs and identify molecules critical for Trm generated in response to acute viral infection. We find that CD8+ TRM across different tissues possess both shared and tissue-specific transcriptional and epigenetic signatures. Notably, Trm in the intestine and salivary gland express TGFb-induced genes and are maintained by ongoing TGFb signaling while those in the fat, kidney, and liver are not. By constructing transcriptional-regulatory networks for each Trm population, we identify the repressor Hic1 as a critical regulator of Trm differentiation, particularly for Trm of the small intestine. This study provides a framework for understanding how Trm adapt to distinct tissue environments and identifies tissue-specific transcriptional regulators that mediate these adaptations, informing strategies to enhance protective memory responses at the sites most vulnerable to infection.
2022-04-18 | GSE182274 | GEO