Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory cells
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE182645 | GEO | 2022/02/01
REPOSITORIES: GEO
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Project description:To evaluate the transcriptional responses of effector and memory virus-specific CD8 T cell subsets after primary and secondary influenza infection, we sorted subsets of FluNP 366-374/Db+ CD8+ T cells from the BAL, lung, and spleen at the peak of primary x31 influenza infection (day 10), resting memory (day 30), or 3 days after secondary PR8 influenza challenge (Day 30+3). Cells from the circulation were excluded from BAL and lung based on intravital labeling with anti-CD45. Memory cells from the lung were further separated in TRM and TEM subsets based on expression of CD69 at the day 30 and day 30+3 timepoints. Memory cells from the BAL were separated into long-term airway resident versus recently-recruited cells based on CD11a expression at the day 30 and days 30+3 timepoints. The results show that virus-specific BAL and lung TRM cells, but not lung TEM cells or spleen TEM cells, rapidly alter their transcriptional program and increase expression of effector molecules within 3 days of a secondary influenza challenge.
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Project description:To determine whether persistent antigen in AdNP immunized mice has any potential cell-intrinsic effects on the genetic program of lung TRM that result in their enhanced longevity, we compared the transcriptional profiles of influenza NP-specific lung TRM (CD8+ i.v. antibody- NP+ CD69+ CD103+), lung TRM that were CD69 single positive (CD8+ i.v. antibody- NP+ CD69+ CD103-) and splenic TEM (CD8+ CD62L- NP+) from mice either infected with x31 influenza or immunized with AdNP at 1-month (35 days post-infection (d.p.i.), x31 and AdNP) and 1-year (365 d.p.i., AdNP only) time points.
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Project description:CD8 tissue-resident memory T cells (TRM) provide frontline immunity in mucosal tissues. The mechanisms regulating CD8 TRM maintenance, heterogeneity, protective and pathological functions are largely elusive. Here we identify an epitope-specific CD8 TRM population that is maintained by in situ MHC-I and B7 signaling following acute influenza infection. These TRM cells co-exhibit exhausted-like phenotypes and memory features, and provide heterologous immunity against secondary infection. PD-L1 blockade at the memory stage promotes exhausted-like TRM rejuvenation and secondary immunity at the cost of developing post-infection fibrotic sequelae. Increased numbers of CD8 TRM cells are observed in the lungs of pulmonary fibrosis patients compared to control patients. Thus, TRM exhaustion results from a tissue-specific cellular adaptation to balance fibrotic sequelae and secondary immunity.
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Project description:T cell factor 1 (Tcf1, encoded by Tcf7) promotes the central memory CD8+ T cell (TCM) differentiation and homeostatic proliferation in lymphoid tissues. It remains unclear if and how Tcf1 regulates the CD103high tissue-resident memory CD8+ T cell (TRM) formation in non-lymphoid tissues. Using an influenza A infection mouse model, we collected Tcf7-deficient and -sufficient lung CD8+ TRM cells for RNA sequencing analysis.
2020-03-16 | GSE135309 | GEO
Project description:Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-β signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa. 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of γδ-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of αβ-DETC from naive TCRδ-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.
2013-10-01 | E-GEOD-47045 | biostudies-arrayexpress
Project description:Lung resident memory (Trm) CD8 T cells induced by influenza A virus (IAV), are pivotal for providing heterosubtypic immunity, but are not maintained long term, causing gradual loss of protection. This contrasts sharply with long-term maintenance of Trm induced by localized infections of the skin and other tissues. Here we show that the decline in lung Trm is determined by an imbalance between apoptosis and lung recruitment/conversion to Trm of circulating memory cells. At the cellular level, circulating effector memory (Tem) rather than central memory (Tcm) cells are the precursors for conversion to lung Trm. Time-dependent changes in expression of genes critical for Trm differentiation together with enrichment of Tcm diminish the capacity of circulating memory CD8 T cells to form Trm, explaining why IAV-induced Trm are not stably maintained over time. Importantly, systemic booster immunization, through increasing the number of circulating Tem cells, induces an increase in lung Trm pool, providing a new rational for future IAV vaccines.
2016-11-18 | GSE86973 | 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
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2023-10-24 | PXD032054 | Pride
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.
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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.
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