Engagement of ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA768793 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16206462_1.fastq.gz | Fastqsanger.gz | |||
| SRR16206462_2.fastq.gz | Fastqsanger.gz | |||
| SRR16206463_1.fastq.gz | Fastqsanger.gz | |||
| SRR16206463_2.fastq.gz | Fastqsanger.gz | |||
| SRR16206464_1.fastq.gz | Fastqsanger.gz |
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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:Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8+ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos-/- CD8+ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8+ Trm cells but not their maintenance. ICOS ligation during CD8+ T cell priming did not determine Trm induction; rather, effector CD8+ T cells showed reduced Trm differentiation after seeding into Icosl-/- mice. IcosYF/YF CD8+ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos-/- Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8+ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.
| S-EPMC8755622 | biostudies-literature
Project description:Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is under strict control of T cell antigen receptor (TCR)-engagement and the skin tissue microenvironment. We here examined the relationship between CCR8+ and CCR8− T cells. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T (TRM) cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue-localization (CD103) and -retention (CD69) markers, low levels of inhibitory receptors (PD-1, Tim-3, LAG-3), and a lack of senescence markers (CD57, KLRG1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (PD-1+), senescent (CD57+, KLRG1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput analyses of expressed T cell receptor beta-chain (TRB) gene rearrangement sequences showed that the two skin memory T cell compartments distinguished by CCR8 expression are clonotypically distinct, suggesting that they are produced in response to separate antigenic challenges and distinct stimulatory conditions. Moreover, the phenotypic profiles of these populations were stable in vitro and the presence of similar levels of telomere erosion excludes the possibility of a linear differentiation pathway. In conclusion, CCR8 marks skin-specific, long-lived memory T cells. Therefore, we propose that CCR8+ T cells should be targeted in future skin vaccination research.
2017-12-11 | E-MTAB-6370 | biostudies-arrayexpress
Project description:During persistent antigen stimulation, PD-1+CD8 T cells are maintained by progenitor exhausted PD-1+TCF-1+CD8 T cells (Tpex). Tpex respond to PD-1 blockade, and regulation of Tpex differentiation into more functional Tex is of major interest for cancer immunotherapies. Tpex express high levels of Inducible Costimulator (ICOS), but the role of ICOS for PD-1+CD8 T cell responses has not been addressed. In chronic infection, ICOS-deficiency increased both number and quality of virus-specific CD8 T cells, with accumulation of effector-like Tex due to enhanced survival. Mechanistically, loss of ICOS signaling potentiated FoxO1 activity and memory features of Tpex. In mice with established chronic infection, ICOS-Ligand blockade resulted in expansion of effector-like Tex and reduction in viral load. In a mouse model of hepatocellular carcinoma, ICOS inhibition improved cytokine production by tumor-specific PD-1+CD8 T cells and delayed tumor growth. Overall, we show that ICOS constrains CD8 T cell responses during chronic antigen exposure.
2025-07-07 | GSE270420 | GEO
Project description:During persistent antigen stimulation, PD-1+CD8 T cells are maintained by progenitor exhausted PD-1+TCF-1+CD8 T cells (Tpex). Tpex respond to PD-1 blockade, and regulation of Tpex differentiation into more functional Tex is of major interest for cancer immunotherapies. Tpex express high levels of Inducible Costimulator (ICOS), but the role of ICOS for PD-1+CD8 T cell responses has not been addressed. In chronic infection, ICOS-deficiency increased both number and quality of virus-specific CD8 T cells, with accumulation of effector-like Tex due to enhanced survival. Mechanistically, loss of ICOS signaling potentiated FoxO1 activity and memory features of Tpex. ICOS-deficient Tex displayed enhanced survival and improved cytokine production. In chronically-infected mice, ICOS-Ligand blockade expanded effector-like Tex, reduced viral load and potentiated anti-PD-L1 therapy. In a mouse model of hepatocellular carcinoma, ICOS inhibition improved cytokine production by tumor-specific PD-1+CD8 T cells and sensitized tumors to PD-1 targeted therapy. Overall, we show that sustained ICOS costimulation limits CD8 T cell responses during chronic antigen exposure.
2025-07-07 | GSE288889 | GEO
Project description:Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood. The central mediator of progressive allergic asthma is allergen-specific, T helper 2 (Th2) resident memory cells (TRMs). However, whether the immature lung facilitates residence of Th2-TRMs is unknown. Employing a mouse model of progressive allergic inflammation from neonates to adults, we found that maturing sympathetic nerves enable a dopamine-enriched lung environment in early life that promotes establishment of allergen-specific Th2-TRMs. To expore the molecular mechanism, we apply bulk RNA-seq to test the transcriptome changes in mouse Th2 cells after dopamine treatment.
2023-06-01 | GSE219287 | GEO
Project description:Engagement of the ICOS receptor represents a key event in a process that culminates in Bcl6 expression and acquisition of the TFH and TFR phenotype. To better understand the essentials of ICOS-mediated signaling pathway, we profiled the changes in gene expression elicited after co-ligation of ICOS and CD3 compared with CD3 ligation alone. Naïve CD4+ T-cells were purified from single cell suspensions of B6 spleen and stimulated with anti-CD3 and anti-CD28 for 2d followed by resting overnight before 20 min of incubation with anti-CD3 and/or anti-ICOS and cross-linking with goat anti-hamster Ab for 8h. RNA was prepared, amplified, labeled and hybridized to Mouse Gene 1.0 ST Array (Affymetrix), in quadruplicates for anti-CD3 ligation and duplicates for anti-CD3/ anti-ICOS co-ligation.
2014-09-23 | E-GEOD-61284 | biostudies-arrayexpress
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
Project description:Engagement of the ICOS receptor represents a key event in a process that culminates in Bcl6 expression and acquisition of the TFH and TFR phenotype. To better understand the essentials of ICOS-mediated signaling pathway, we profiled the changes in gene expression elicited after co-ligation of ICOS and CD3 compared with CD3 ligation alone.
2014-09-23 | GSE61284 | GEO
Project description:CD8 Tissue Resident Memory (TRM) induction
| PRJNA1036221 | ENA