A4b7 engagement triggers CD4+ T cell differentiation into TRM cells that are susceptible to HIV infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA914297 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We report that MAdCAM and retinoic acid (RA), two constituents of gut tissues, together with TGF-b, promote the differentiation of CD4+ T cells into a distinct subset a4b7+ CD69+ CD103+ TRMs. These findings provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.
2022-12-21 | GSE221434 | GEO
Project description:Recirculating and tissue-resident memory CD8+ T cells provide distinct modes of immune protection, yet the signals that dictate differentiation of these populations are ill-defined. In particular, the interactions within tissues that promote generation of resident memory T cells (TRM) are unclear. Here, we show that the inducible costimulatory molecule ICOS, well known to regulate differentiation of CD4+ T cell populations, is required for CD8+ TRM but not recirculating memory subsets. Furthermore, ICOS engagement during CD8+ T cell recruitment to non-lymphoid tissues is critical for efficient TRM establishment: ICOS/ICOS-L interactions are dispensable throughout CD8+ T cell priming and for TRM maintenance, while ICOS-L expression by radioresistant cells is key for optimal TRM generation. This role for ICOS depends on its ability to signal through PI3K. Together, our data illustrate that specific local costimulatory cues promote production of tissue-resident populations, with potential implication for therapeutic manipulation.
2021-12-20 | GSE185342 | GEO
Project description:Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRMlike profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIVspecific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.
2022-10-12 | GSE215125 | GEO
Project description:Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRMlike profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIVspecific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.
2022-10-12 | GSE215126 | GEO
Project description:Tissue-resident memory CD8+ T cells (TRM) constitute a non-circulating memory T cell subset that provides early protection against re-infection. However, how TRM arise from antigen-triggered T cells has remained unclear. Exploiting the TRM-restricted expression of Hobit, we developed TRM reporter/deleter mice to study TRM differentiation. We found that Hobit was upregulated in a subset of LCMV-specific T cells located within peripheral tissues during the effector phase of the immune response. These Hobit+ effector T cells were identified as TRM precursors, given that their depletion substantially decreased TRM development, but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit+ effector T cells corroborated their biased contribution to the TRM lineage. Transcriptional profiling of Hobit+ effector T cells underlined the early establishment of TRM properties including downregulation of tissue exit receptors and upregulation of TRM-associated molecules. Importantly, we identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of TRM occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.
2021-08-19 | GSE182343 | GEO
Project description:The ability to detect and isolate human CD8 TSP (Side population), Naïve, Effector memory (EM), Central memory (CM) cells allowed us to compare the global gene expression profiles of these cells. Human TSP cells comprise of distinct gene expression profile specifically enriched for genes overexpressed in TRM cells. RNA samples from CD8 TSP (Side population), Naïve, Effector memory (EM), Central memory (CM) cells were amplified, labeled, and hybridized on the Affymetrix Human Genome U133 Plus 2.0 microarray chips. The data were analyzed with GeneSpring GX 12.5 (Agilent Technologies)
2016-08-02 | E-GEOD-85074 | biostudies-arrayexpress
Project description:To address both the plasticity of intestinal Trm subsets and their unique contributions to tissue and systemic immunity, we have generated mice to fate map CD103+ Trm cells after primary infection and follow their location and functionality during secondary infection. We found that the intestinal CD103– Trm subset are the primary responders to secondary infection and observed limited expansion of the CD103+ Trm subset. To understand the unique features of CD103– Trm cells that allow this population to respond more quickly to secondary infection and to understand the gene expression changes that accompany Trm reactivation, we performed RNA-sequencing on CD103+Tomato+ and CD103–Tomato– LP Trm cells.
2022-09-12 | GSE185541 | GEO
Project description:The aim of the experiment was to understand the clonal relationship between CD8+ central memory blood T cells (TCM) and the in-vivo matured TCM tissue-resident memory-like T cells (TRM) on day 14. TCM were FACS sorted from human PBMCs (n=5). Half of the cells were processed on day 1 and half of the cells of each donor were matured into TRM with anti-CD3, IL-15 and TGF beta for 14 days. Both day 1 TCM and matured day 14 TRM-like cells were further processed using the 5´10X genomics workflow.
2023-06-12 | E-MTAB-12840 | 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:CD8+ TRM are described in autoimmune and chronic inflammatory diseases. However, we still lack knowledge about mechanisms regulating TRM reactivation, in particular in autoimmune diseases. Here, we investigated in a model of TRM-driven central nervous system autoimmunity the transcriptional landscape of self-reactive brain TRM and the requirement of these cells for CD4+ T cell help.
2023-01-25 | GSE189580 | GEO