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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

ABSTRACT: Global profiling to investigate the consequence of the lack of TAP-1 on hematopoetic cell or non-hematopoetic cell on the qualitative response of reactivated antigen-specific Trm cells

ORGANISM(S): Mus musculus

PROVIDER: GSE147906 | GEO | 2020/04/02

REPOSITORIES: GEO

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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

Project description:Temporal transcriptome profiling of TCR-reactivated (P14) and bystander-reactivated (OT-I) memory T cells in the lung and mediastinal lymph node based on Nur77-GFP reporter expression and CD98 expression

2020-04-02 | GSE147907 | GEO

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses.

Project description:CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing TRM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish "antigen-specific" from "bystander" reactivation, we demonstrate that lung CD8+ TRM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (TLN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ TLN cells, which is strictly dependent on CD11c+XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ TRM cells, but the quality of TRM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.

| S-EPMC7398161 | biostudies-literature

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-02 | GSE147908 | GEO

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

| PRJNA622522 | ENA

Molecular signature of brain resident memory CD8+ T cells

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

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

| PRJNA622525 | ENA

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

Project description:Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

| PRJNA622526 | ENA

An unconventional integrin b3 and CD103 heterodimer improves the anti-tumor immunity of tissue-resident T cells

Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.

2024-02-14 | PXD031794 | Pride

Clonotypic analysis of protective influenza M2e-specific lung resident T helper memory cells reveals extensive functional plasticity

Project description:Intranasal influenza immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 tissue resident memory (Trm) cells that conferred strong antibody-independent protection against infection at 6 months after priming. These cells rapidly expanded in the lung upon infection and effectively restricted virus replication. Single-cell RNAseq transcriptomic and TCR VDJ-analysis of M2e- tetramer-sorted Trm cells on day 3 and 8 post infection revealed complete Th17-lineage dominance (no Th1, Tfh or Foxp3+ Tregs) with extensive functional plasticity involving cytotoxicity (ThCTL) as well as regulatory functions. Unexpectedly, the same clonotype hosted cells with different Th17 subcluster functions (IL-17, IL-22), Tr1 cells and ThCTLs, suggesting a tissue and context-dependent differentiation of reactivated Th17 Trm cells. A gene set enrichment analysis demonstrated up- regulation of regulatory genes in the day 8 recovery phase. Contrary to present thinking lung M2e- specific Th17 Trm cells are sufficient for controlling infection and for preventing tissue injury. These findings will have strong implications for vaccine development.

2022-06-29 | GSE161938 | GEO

Tissue resident memory T cells trigger rapid exudation and local antibody accumulation

Project description:Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in the mouse female genital tract increased local concentrations of virus-specific neutralizing antibodies including anti-vesicular stomatitis virus and passively transferred anti-HIV antibodies. We showed that this response was sufficient to increase the efficacy of ex vivo vesicular stomatitis virus neutralization. These results indicate that CD8+ TRM antigen recognition can enhance local humoral immunity. Microarray data comparing RNA isolated from murine female reproductive tract tissue from control tissue (SIIN) versus tissues where resident memory T cells were reactivated 9 hours prior (GP33). Control mice (SIIN) received the irrelevant peptide SIINFEKL transcervically. Experimental mice (GP33) recieved the peptide gp33, which P14 resident memory T cells specifically recognize, transcervically.

2022-12-09 | GSE219002 | GEO

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