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Surface CD69-negative bone-marrow resident human memory T cells [ESR transcription]

ABSTRACT: Surface CD69-negative bone-marrow resident human memory T cells [ESR transcription]

PROVIDER: PRJNA1166208 | ENA |

REPOSITORIES: ENA

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Surface CD69-negative bone-marrow resident human memory T cells [ESR TCR]

Project description:Across tissues, tissue-resident memory T cells have been defined as cells which express CD69 in their cell surface, but not S1PR1, the receptor for the tissue-egress signal sphingosin-1-phosphate (S1P). It is less clear whether CD69-negative memory T cells are also tissue-resident. Here, we compare transcriptomes and T cell receptor repertoires of individual CD4 and CD8 memory T cells from paired blood and bone marrow of three human donors. CD69- memory T cells of blood and bone marrow share transcriptionally defined clusters, as defined by signature genes reflecting their imprinting during activation. However, cells of related clusters of blood and bone marrow have distinct TCR repertoires, suggesting that they represent distinct compartments of memory, and that the CD69- memory T cells are residents of the bone marrow. Interestingly, the surface CD69- memory T cells of bone marrow do transcribe the CD69 gene, and they express S1PR1, suggesting that they are blindfolded for S1P by dimerization and internalization of CD69 and S1PR1, maintaining them in the tissue.

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Surface CD69-negative bone-marrow resident human memory T cells [ESR transcription]

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Surface CD69-negative bone-marrow resident human memory T cells [ESR TCR]

Project description:Surface CD69-negative bone-marrow resident human memory T cells [ESR TCR]

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CD69+ memory T lymphocytes of the bone marrow and spleen express the signature transcripts of tissue-resident memory T lymphocytes

Project description:To understand tissue resident features of memory CD4+ and CD8+ T lymphocytes of the bone marrow and/or spleen according to expressing or not the tissue retention marker CD69, we performed whole transcriptome profiling of ex vivo antigen-specific CD69+ and CD69- memory CD4+ T cells isolated from bone marrow and spleen, and ex vivo CD69+ and CD69- memory CD8+ T cells isolated from bone marrow.

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Whole-transcriptome profiling of murine steady state CD69+ and CD69- memory CD8+ T cells from the bone marrow [expression microarray]

Project description:To understand the tissue-resident features of memory CD8+ T cell subpopulations isolated from the bone marrow according to the tissue retention marker CD69, we compared the global gene expression of ex vivo isolated CD69+ and CD69- bone marrow memory CD8+ T cells.

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Kidney-resident CD8 T cells downregulate IL-18R during maturation

Project description:Using the expression of IL-18 receptor (CD218) as a surface marker, CD69+ kidney-resident CD8 T cells can be separated into two subsets. Transcriptional analysis suggests that IL-18R low subset represents the mature tissue-resident T cells

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mRNA profiles of Salmonella specific tissue resident memory CD4 T cells and effector memory CD4 T cells from the liver, and splenic effector memory CD4 T cells

Project description:IFN -YFP reporter mice (Jax# 017580) were immunized intravenously with attenuated Salmonella enterica serovar Typhimurium intravenously. 45 days later, tissue resident memory CD4 T cells (CD69+ YFP+) in the liver, effector memory CD4 T cells (CD69- YFP+) in the liver, and effector memory CD4 T cells (CD69- YFP+) in the spleeen were sorted and RNA was sequenced

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Project description:Lung resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts have yet to be determined, as has their functional significance. We postulate that BRM cells are core components of lung immunity. To test this, we examined whether lung BRM cells are elicited by the respiratory pathogen pneumococcus, are present in humans, and are important in pneumonia defense. Lungs of mice recovered from pneumococcal infections did not contain organized lymphoid structures, but did have non-circulating memory B cells that expressed distinctive surface markers (including CD69, PD-L2, CD80, and CD73) and were poised to secrete antibodies upon stimulation. Human lungs also contained B cells with a resident memory phenotype. In mice recovered from pneumococcal pneumonia, depletion of PD-L2+ B cells, including lung BRM cells, drastically compromised bacterial clearance. These data define lung BRM cells as a common feature of pathogen-experienced lungs and provide direct evidence of a role for these cells in pulmonary anti-bacterial immunity.

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CD69-dependent gene expression in activated CD4 T cells from the spleen of Mus musculus

Project description:CD69 is a transmembrane protein expressed on the surface of activated leukocyte. The ligand for CD69 and the intracellular signaling pathway of this molecule are yet unknown. It is widely used as a marker of activated lymphocyte, but its function in immune system is not known. We used micro-array to define genes whose expression is regulated by activation antigene CD69. CD4 T cells were isolated from the spleen of wt B6 and CD69-deficient B6 mice and in vitro activated with anti-CD3/anti-CD28 coated beads. On one groupe of wt B6 cells, CD69 was activated using a anti-CD69 and secoundary antibody. RNA extraction and hybridization on Affymetrix microarrays was performed for wt B6, CD69-activated wt B6 and CD69-deficient B6 CD4 T cells.

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CCR8 expression defines tissue-resident memory T cells in human skin

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.

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