KLRG1+ Memory CD8 T cells Combine Properties of Short-lived Effectors and Long-lived Memory
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PROVIDER: PRJNA640616 | ENA |
REPOSITORIES: ENA
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Project description:CD8 effector T cells with a CD127hi KLRG1- phenotype are considered precursors to the long-lived memory pool, while KLRG1+ CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+ CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells or LLEC) display robust protective function during acute re-challenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. Here, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. Furthermore, we find that LLEC are exclusively derived from day 12 KLRG1+ effector cells. Our work challenges the concept that the KLRG1+ CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell.
2020-08-26 | GSE152841 | GEO
Project description:The goal of this study is to characterize the transcriptional profile of three memory CD8 T cell subsets: IL-7Rα+KLRG1- (memory precursors, MP), IL-7Rα+KLRG1+ (KLRG1+ MP) and IL-7Rα-KLRG1+ (terminal effectors, TE).
2022-12-12 | GSE218777 | GEO
Project description: Not available
| S-EPMC7415731 | biostudies-literature
Project description:During acute viral infections in mice, IL-7Rα and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7RαloKLRGhi) from the precursors of persisting memory cells (MPEC; IL-7RαhiKLRG1lo). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in ‘steady state’ in humans. In contrast to the T cells in the circulation, T cells derived from lymph nodes hardly contain any KLRG1-expressing cells. The four populations defined by IL-7Rα and KLRG1 differ markedly in transcription factor, granzyme and chemokine receptor expression. When studying renal transplant recipients experiencing a primary hCMV and EBV infection, we also found that after viral control, during latency, Ki-67-negative SLEC can be found in the peripheral blood in considerable numbers. Thus, combined analyses of IL-7Rα and KLRG1 expression on human herpes virus-specific CD8+ T cells can be used to separate functionally distinct subsets in humans. As a non-cycling IL-7RαloKLRG1hi population is abundant in healthy humans, we conclude that this combination of markers not only defines short-lived effector cells during the acute response but also stable effector cells that are formed and remain present during latent herpes infections.
2019-02-01 | GSE113098 | GEO
Project description:The events controlling transition of T cells from effector to memory remain poorly understood. Herein, we defined two types of effectors on the basis of cell division, expression of activation markers and production of effector cytokines and investigated their potential for memory generation. The results indicated that the moderately activated early effectors readily transit to memory while highly activated late effectors develop minimal memory. Boosting with antigen-free adjuvant, however, rescues the late effectors from cell death and sustains both survival and cytokine responses through toll-like receptor function. Also, the genome-wide microarray analysis among early and late effectors pointed to a set og defined as well as less known genes that may play a role in transition to memory. CFSE-labeled DO11.10 CD4 naïve T cells were transferred into Balb/c mice and the hosts were immunized with OVA peptide in CFA. Within 3 days, the lymph node cells were harvested and each effector division (from division 2 to 8) was sorted based on CFSE dilution and then they were either transferred into naive hosts to generate memory cells or their RNAs were extracted to perform genome-wide microarray analysis. To correlate gene expression with memory potential, division 4 (D4), which readily transit to memory, and divisions 3 (D3), 6 (D6) and 8 (D8), which display reduced potential for memory transition, were included. The data were derived from 3 independent experiments (3 samples per division, 12 samples total).
2011-01-01 | E-GEOD-25141 | biostudies-arrayexpress
Project description:The events controlling transition of T cells from effector to memory remain poorly understood. Herein, we defined two types of effectors on the basis of cell division, expression of activation markers and production of effector cytokines and investigated their potential for memory generation. The results indicated that the moderately activated early effectors readily transit to memory while highly activated late effectors develop minimal memory. Boosting with antigen-free adjuvant, however, rescues the late effectors from cell death and sustains both survival and cytokine responses through toll-like receptor function. Also, the genome-wide microarray analysis among early and late effectors pointed to a set og defined as well as less known genes that may play a role in transition to memory.
2011-01-01 | GSE25141 | GEO
Project description:Memory B cells represent one of the pillar of humoral protection and are found in the circulation and secondary lymphoid organs several decades after initial pathogen or vaccine encounter. The exact cellular and biological mechanisms allowing long-term survival of quiescent cells in such a fluctuating microenvironment remain poorly understood. Assessing the true longevity of human memory B cells against common pathogens is, in most settings, hindered by the possibility for any given individual to re-encounter them during his lifetime. Smallpox, officially declared eradicated in 1980 (Fenner WHO 1988), represents one notable exception. Alongside smallpox eradication, anti-smallpox vaccination, based on the live Vaccinia virus, was progressively discontinued during the 1970s. As such, any detectable anti-vaccinia memory B cell in an individual post 2010 would likely have been generated more than 40 years ago, without any re-stimulation with the immunizing antigen during that timeframe. Anti-vaccinia antibodies serum titers remain stable in human for more than 80 years after first vaccination (Amanna NEJM 2007, PMID: 17989383), with several identified immunodominant epitopes including the envelope glycoprotein B5R (Lantto J Virol 2011, PMID: 21147924). Anti-vaccinia memory B cells have similarly been followed longitudinally in the blood for up to 65 years post vaccination (Amanna NEJM 2007, PMID: 17989383 ; Crotty JI 2003, PMID : 14607890) and, following a contraction phase taking place in the first couple of years after immunization, reach a remarkably stable plateau that last for decades at around 0.1% of total circulating IgG+ memory B cells. Functional analysis of such long-lived memory B cells, however, is still lacking. As a proxy to study long-lived memory B cells, IgG+ switched memory B cells specific for the immunodominant Vaccinia antigen B5R (B5R+ IgG+ memory B cells) were sorted and analyzed by scRNAseq from the spleen of six organ donors, collected between 2015 and 2018. For all donors, B5R+ IgG+ memory B cells were sorted alongside total IgG+ memory B cells (live IgD-CD27+IgG+CD20+CD3-CD14-CD16-) and naïve B cells (live IgD+CD27-CD38-CD24-CD20+CD3-CD14-CD16-). Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, PMID: 27693023), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).
2022-09-19 | E-MTAB-11626 | biostudies-arrayexpress
Project description:KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate Into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity
| PRJNA434329 | ENA
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:Purpose: RNA-seq analysis of three memory OT-I cell subsets (from a Klrg1-Cre fate reporter mouse model) isolated from the spleen of C57BL/6 mice infected with Listeria monocytogenes. The hypothesis tested in the present study was that KLRG1+ effector CD8 T lymphocytes differentiate into KLRG1- memory CD8 T lymphocytes and provide long-lasting immunity against infectious diseases and malignancies. Methods: Total RNA was obtained from FACS-purified OT-I cell subsets isolated from spleen 104 (experiment 1) and 110 days post infection (experiment 2) with ovalbumin-expressing Listeria monocytogenes (LM-OVA). Results: Using RNA-seq technology, we performed genome-wide transcriptional profiling of three memory OT-I cells (KLRG1+ Reporter+, KLRG1- Reporter+ (exKLRG1) and KLRG1- Reporter-) and identified 36 genes differentially expressed (> 1.5-fold) between exKLRG1 and KLRG1- Reporter- memory OT-I cells, and 132 differentially expressed genes between exKLRG1 and KLRG1+ Reporter+ memory OT-I cells. We then confirmed the expression of 15 genes/molecules by qRT-PCR and/or flow cytometry. Conclusions: Our study represents the first fate mapping analysis of KLRG1+ effector OT-I cells, demonstrates that KLRG1+ effector OT-I cells differentiate into all memory T cell lineages thereby promoting protective immunity. RNA-seq also identified CX3CR1 as a marker of circulating exKLRG1 early memory OT-I cells.
2018-03-01 | GSE110629 | GEO