Human CMV-specific vs IAV-specific CD8 T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171246 | GEO | 2022/11/21
REPOSITORIES: GEO
Similar Datasets
Project description:We compared CD8 TCM cells specific for a CMV epitope (pp65495-503) and an influenza A virus (IAV) epitope (M158-66) of the same healthy adults and identified genes whose expression are altered in CMV-specific compared to IAV-specific TCM cells.
2022-11-30 | GSE200258 | GEO
Project description:Human CMV-specific vs IAV-specific CD8 TCM cells
| PRJNA823760 | ENA
Project description:Human CMV-specific vs IAV-specific CD8 T cells
| PRJNA718851 | ENA
Project description:Reconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary.
2015-01-28 | GSE61927 | GEO
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:Reconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary. C57BL/6 mice were infected intraperitoneally (i.p.) with MCMV strain MW97.01 between 6-16 weeks of age. Splenocytes were isolated from chronically-infected mice and co-stained with three PE-conjugated tetramers loaded with the antigenic peptides from M38, m139 and IE3, all of which promote memory inflation. Cells were then stained with fluorescently conjugated antibodies and sorted on a MoFlo cell sorter. Naïve CD8+ cells were identified as CD44lo. MCMV-specific T cells were identified as CD8+, CD44hi and tetramer binding and then further segregated into memory and effector cells subsets by their expression of KLRG1 and CD127.
2015-01-28 | E-GEOD-61927 | biostudies-arrayexpress
Project description:The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the MHC (pMHC) on cells is an essential parameter for efficient T cell-mediated immunity. Yet, whether the TCR-ligand avidity can drive the clonal evolution of virus antigen-specific CD8 T cells, and how this process is determined in latent Cytomegalovirus (CMV)- against Epstein-Barr virus (EBV)-mediated infection remains largely unknown. Here, we quantified monomeric TCR-pMHC dissociation rates on CMV- and EBV-specific individual TCR-alpha-beta clonotypes and polyclonal CD8 T cell populations in healthy donors over a follow-up time of 15-18 years. Within CMV/pp65-specific T cell repertoires, a progressive contraction of clonotypes with high TCR-pMHC avidity and low CD8 binding dependency was observed, leading to an overall avidity decline during long-term antigen exposure. We identified a unique transcriptional signature preferentially expressed by high-avidity CMV/pp65-specific T cell clonotypes, including the inhibitory receptor LILRB1. Interestingly, T cell clonotypes of high-avidity showed higher LILRB1 expression than the low-avidity ones and LILRB1 blockade moderately increased T cell proliferation. Similar findings were made for CD8 T cell repertoires specific for the CMV/IE-1 epitope. There was a gradual in vivo loss of high-avidity T cells with time for both CMV specificities, corresponding to virus-specific CD8 T cells expressing enhanced LILRB1 levels. In sharp contrast, the EBV/BMFL1-specific T cell clonal composition and distribution, once established, displayed an exceptional stability, unrelated to TCR-pMHC binding avidity or LILRB1 expression. Together, these findings reveal an overall long-term avidity decline of CMV- but not EBV-specific T cell clonal repertoires, highlighting the differing role played by TCR-ligand avidity over the course of these two latent herpesvirus infections. Our data suggest that the inhibitor receptor LILRB1 potentially restricts the clonal expansion of high-avidity CMV-specific T cell clonotypes during latent infection. We propose that the mechanisms regulating the long-term outcome of CMV- and EBV-specific memory CD8 T cell clonotypes in humans are distinct.
2023-11-15 | GSE246111 | GEO
Project description:Analysis of global gene expression profiles of FACS-sorted, human Ad5- and CMV-specific CD4 T cells from the same PBMC sample of healthy donros, using affymetrix Human Gene 2.0ST Gene-Chips; The analysis show that Ad5- and CMV-specific CD4 T cells demonstrate differential gene expression profiles even though the cells are from the same PBMC
2014-08-07 | GSE60180 | GEO
Project description:Infection with cytomegalovirus is characterised by very strong and sustained T cell responses in peripheral blood. These expansions increase even further with age and research suggests CMV-specific T cells may contribute towards development of accelerated immune senescence and vascular disease in elderly people. In this study we compared the transcriptional profile of CD4+ T cells specific for two CMV-derived epitopes to that of CD4+CCR7-CD45RA- (effector memory) T cells of CMV-seronegative individuals. The aim was to get a better understanding of the nature of these virus-specific T cells and how they may contribute to immunopathology.
2016-08-07 | E-MTAB-4510 | biostudies-arrayexpress
Project description:Analysis of global gene expression profiles of FACS-sorted, human Ad5- and CMV-specific CD4 T cells from the same PBMC sample of healthy donros, using affymetrix Human Gene 2.0ST Gene-Chips; The analysis show that Ad5- and CMV-specific CD4 T cells demonstrate differential gene expression profiles even though the cells are from the same PBMC PBMC from healthy donors (n=3) were CFSE-labeled, then equally divided and stimulated with Ad5 and CMV antigens; On day 6 post stimulation, Ag-specific CD4 T cells were sorted by flow based on CFSE-low.
2014-08-07 | E-GEOD-60180 | biostudies-arrayexpress