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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Skin Resident Memory CD4+ T Cells Enhance Protection Against Leishmania Major Infection

ABSTRACT: Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection following disease resolution, effective immune protection has not yet been achieved by human vaccines. While circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFNγ, and remain resident in the skin when transplanted by skin graft onto naïve mice. They function to recruit circulating T cells to the skin in a CXCR3 dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells. Two conditions were analyzed. For each condition, four mice were used, resulting in eight samples in total.

ORGANISM(S): Mus musculus

SUBMITTER: daniel beiting

PROVIDER: E-GEOD-69998 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Skin Resident Memory CD4+ T Cells Enhance Protection Against Leishmania Major Infection

Project description:Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection following disease resolution, effective immune protection has not yet been achieved by human vaccines. While circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFNγ, and remain resident in the skin when transplanted by skin graft onto naïve mice. They function to recruit circulating T cells to the skin in a CXCR3 dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.

2015-06-19 | GSE69998 | GEO

Mus musculus

Project description:Skin Resident Memory CD4+ T Cells Enhance Protection Against Leishmania Major Infection

| PRJNA287436 | ENA

RNA-seq data of lung resident T-cells from mice following house dust mite (HDM) sensitisation and subsequent influenza virus challenge

Project description:This data is from a murine model established to study the lasting impact of allergic airway sensitization on subsequent anti-viral memory T cell responses and the ability to develop protective immunity to reinfection. Animals were either sensitised by exposure to HDM or PBS and then subsequently exposed to influenza virus. Samples were collected at various time points for analysis of both CD8 and C4 positive tissue resident memory T cells.

2023-01-30 | E-MTAB-11116 | biostudies-arrayexpress

Single-cell RNA-seq of ex vivo CD45-negative skin resident-cells using microfluidic droplet capture

Project description:To obtain a large representation of non-immune skin-resident cells, we profiled CD45-negative cells from a digested skin sample taken from a human female

2018-07-06 | E-MTAB-6831 | biostudies-arrayexpress

Dynamic equilibrium of lung Trm dictates waning immunity after IAV infection

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

scRNA-seq of murine effector CD8 T cells in response to local vaccination

Project description:Mice received barcode-labelled OT-I T cells and were challenged with a DNA vaccine, encoding the OVA peptide, which was applied locally on the skin of the hind legs. 12 days after vaccination, we performed single cell RNA sequencing on circulating effector CD8+ T cells (isolated from blood). We detected cells which transcriptionally resemble mature tissue resident memory T cells.

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Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation.

Project description:To investigate the transcriptional profile of human circulating T cells with skin tissue-resident memory phenotype (cTRM) in GVHD we performed bulk RNA sequencing from SMART-seq2 of sorted human cTRM (CD3+ CD4+ CLA+ CD103+) and conventional T cells (CD3+ CD4+ CD103-), and single cell RNA sequencing from 10X Genomics of sorted human CD45+, both from isolated blood PBMCs of patients with active acute GVHD.

2021-09-24 | GSE183212 | GEO

Expression data from circulating and lung tissue resident memory CD4 T cell responding towards infuenza A virus infection

Project description:How tissue resident memory CD4 T cell differ from circulating memory CD4 T cells and how such differences impact functional recall responses to pathogens is unknown. We used microarrays to detail the global programme of gene expression underlying differences between sort purified circulating memory CD4 T cells from the lung and spleen, which are labelled with flourescent antibody following intravenous administration, and lung tissue resident memory CD4 T cells, which are not labelled with flourescent antibody following intravenous administration, on day 28 post influenza infection.

2020-10-18 | GSE105257 | GEO

Genome wide transcriptome analysis of skin harboring tissue-resident memory CD8+ T cells

Project description:Comparison of the transcriptional profiles of full-thickness murine skin harboring tissue resident memory T cells exposed to specific or control trigger Expression profiling by high throughput sequencing

2014-09-11 | E-GEOD-60599 | biostudies-arrayexpress

Development pathway for skin resident memory CD103+CD8+ T cells

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)-Î² 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 Î³Î´-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of Î±Î²-DETC from naive TCRÎ´-/- 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

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