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Transcriptional control of influenza-specific CD4+ tissue-resident memory T cell generation

ABSTRACT: Transcriptional control of influenza-specific CD4+ tissue-resident memory T cell generation

PROVIDER: PRJNA565358 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10113100.fastq.gz	Fastqsanger.gz
	SRR10113101.fastq.gz	Fastqsanger.gz
	SRR10113102.fastq.gz	Fastqsanger.gz
	SRR10113103_1.fastq.gz	Fastqsanger.gz
	SRR10113103_2.fastq.gz	Fastqsanger.gz

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Transcriptional control of influenza-specific CD4+ tissue-resident memory T cell generation

Project description:Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation.

2020-09-01 | GSE137386 | GEO

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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.

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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. Two conditions were analyzed. For each condition, four mice were used, resulting in eight samples in total.

2015-06-19 | E-GEOD-69998 | biostudies-arrayexpress

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Project description:Long-lived, tissue-resident memory B cells (BRM) are established in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localised within inducible bronchus-associated lymphoid tissues (iBALT) and displayed phenotypic and transcriptional signatures reminiscent of tissue-resident T cells, distinct from classical memory B cells in the blood or secondary lymphoid sites.

2021-11-18 | GSE159383 | GEO

mRNA profiles of Salmonella specific tissue resident memory CD4 T cells and effector memory CD4 T cells from the liver, and splenic effector memory CD4 T cells

Project description:IFN -YFP reporter mice (Jax# 017580) were immunized intravenously with attenuated Salmonella enterica serovar Typhimurium intravenously. 45 days later, tissue resident memory CD4 T cells (CD69+ YFP+) in the liver, effector memory CD4 T cells (CD69- YFP+) in the liver, and effector memory CD4 T cells (CD69- YFP+) in the spleeen were sorted and RNA was sequenced

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CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses

Project description:This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly utilized residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property-specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells.

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2022-02-01 | GSE182645 | GEO

Deciphering and predicting CD4+ T cell immunodominance of Influenza virus hemagglutinin

Project description:The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naïve and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naïve and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naïve CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naïve T cells specific for cryptic H1-HA peptides, and demonstrate that antigen processing represents a major constraint determining immunodominance.

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Secondary influenza challenge triggers lung resident memory B cell mobilization and rapid relocation for antibody secretion at infected loci

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