CD73+ memory CD4 T cells are a long-lived population with elevated effector function and prone to differentiate into TRM-like cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157164 | GEO | 2021/08/28
REPOSITORIES: GEO
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Project description:The understanding of heterogeneity of human memory T cells will help to know the function, development and maintenance of memory population, then to improve the recall response or effective immunotherapy. Ecto-5’-nucleotidase CD73 expression in four subsets of memory T cells decreases with aging. The resistance to apoptosis and high expression of IL7R entitle CD73+ memory T cells to be long-lived population. We found antigen-specific memory T cells have overwhelming CD73 expression. The transcriptional and chromatin accessibility profiles indicate the elevated effector functions in CD73+ memory CD4 T cells comparing to CD73- counterparts. Homer analysis and Transcriptional factor (TF)-regulatory element-target gene triplet network clearly show the crucial role of RUNT and NR family TFs in CD73+ cells. Furthermore, CD73+ memory CD4 T cells were prone to differentiate into TRM-like cells under in-vitro sequential TCR and TGF/IL-15 signaling. The decreased percentage of CD73+ memory T cells with age leads to the less replenishment of TRM cells from peripheral blood.
2021-08-28 | GSE157163 | GEO
Project description:The understanding of heterogeneity of human memory T cells will help to know the function, development and maintenance of memory population, then to improve the recall response or effective immunotherapy. Ecto-5’-nucleotidase CD73 expression in four subsets of memory T cells decreases with aging. The resistance to apoptosis and high expression of IL7R entitle CD73+ memory T cells to be long-lived population. We found antigen-specific memory T cells have overwhelming CD73 expression. The transcriptional and chromatin accessibility profiles indicate the elevated effector functions in CD73+ memory CD4 T cells comparing to CD73- counterparts. Homer analysis and Transcriptional factor (TF)-regulatory element-target gene triplet network clearly show the crucial role of RUNT and NR family TFs in CD73+ cells. Furthermore, CD73+ memory CD4 T cells were prone to differentiate into TRM-like cells under in-vitro sequential TCR and TGF/IL-15 signaling. The decreased percentage of CD73+ memory T cells with age leads to the less replenishment of TRM cells from peripheral blood.
2021-08-28 | GSE157162 | GEO
Project description:CD73+ memory CD4 T cells are a long-lived population with elevated effector function and prone to differentiate into TRM-like cells
| PRJNA660345 | ENA
Project description:CD73+ memory CD4 T cells are a long-lived population with elevated effector function and prone to differentiate into TRM-like cells [ATAC-seq]
| PRJNA660347 | ENA
Project description:CD73+ memory CD4 T cells are a long-lived population with elevated effector function and prone to differentiate into TRM-like cells [RNA-seq]
| PRJNA660348 | ENA
Project description:T helper 17 (TH17) cells have been shown to contribute to multiple disease systems. However, the functional phenotype and survival pattern of TH17 cells as well as the underlying mechanisms that control TH17 cells have been poorly investigated in humans, significantly hampering the clinical targeting of these cells. Here, we studied human TH17 cells in the pathological microenvironments of graft-versus-host disease, ulcerative colitis, and cancer; TH17 cell numbers were increased in the chronic phase of these diseases. Human TH17 cells phenotypically resembled terminally differentiated memory T cells but were distinct from central memory, exhausted, and senescent T cells. Despite their phenotypic markers of terminal differentiation, TH17 cells mediated and promoted long-term antitumor immunity in in vivo adoptive transfer experiments. Furthermore, TH17 cells had a high capacity for proliferative self-renewal, potent persistence, and apoptotic resistance in vivo, as well as plasticity-converting into other types of TH cells. These cells expressed a relatively specific gene signature including abundant antiapoptotic genes. We found that hypoxia-inducible factor-1? and Notch collaboratively controlled key antiapoptosis Bcl-2 family gene expression and function in TH17 cells. Together, these data indicate that human TH17 cells may be a long-lived proliferating effector memory T cell population with unique genetic and functional characteristics. Targeting TH17-associated signaling pathway would be therapeutically meaningful for treating patients with autoimmune disease and advanced tumor.
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Project description:Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (TRM) cells. However, the cellular origin of CD4 TRM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 TRM cells derive from IL-17A-producing effector (TH17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exTH17 TRM cells are maintained in the lung by IL-7, produced by lymphatic endothelial cells. During a memory response, neither antibodies, ?? T cells, nor circulatory T cells are sufficient for the rapid host defense required to eliminate Kp. Conversely, using parabiosis and depletion studies, we demonstrated that exTH17 TRM cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 TRM cells during bacterial infection, offering novel strategies for targeted vaccine design.
| S-EPMC7057720 | biostudies-literature
Project description:ObjectiveImmunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance.MethodsIn a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry.ResultsBetter cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account.ConclusionsThis is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.
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Project description:Although circulating memory T cells provide enhanced protection against pathogen challenge, they often fail to do so if infection is localized to peripheral or extralymphoid compartments. In those cases, it is T cells already resident at the site of virus challenge that offer superior immune protection. These tissue-resident memory T (T(RM)) cells are identified by their expression of the α-chain from the integrin α(E)(CD103)β(7), and can exist in disequilibrium with the blood, remaining in the local environment long after peripheral infections subside. In this study, we demonstrate that long-lived intraepithelial CD103(+)CD8(+) T(RM) cells can be generated in the absence of in situ antigen recognition. Local inflammation in skin and mucosa alone resulted in enhanced recruitment of effector populations and their conversion to the T(RM) phenotype. The CD8(+) T(RM) cells lodged in these barrier tissues provided long-lived protection against local challenge with herpes simplex virus in skin and vagina challenge models, and were clearly superior to the circulating memory T-cell cohort. The results demonstrate that peripheral T(RM) cells can be generated and survive in the absence of local antigen presentation and provide a powerful means of achieving immune protection against peripheral infection.
| S-EPMC3344960 | biostudies-literature
Project description:Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.
| S-EPMC5965677 | biostudies-literature