Single-cell chimerism and transcriptional profiling identify long-term human skin-resident host T cells after stem cell transplantation
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ABSTRACT:
PROVIDER: PRJNA792150 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17329257_1.fastq.gz | Fastqsanger.gz | |||
| SRR17329257_2.fastq.gz | Fastqsanger.gz | |||
| SRR17329258_1.fastq.gz | Fastqsanger.gz | |||
| SRR17329258_2.fastq.gz | Fastqsanger.gz | |||
| SRR17329259_1.fastq.gz | Fastqsanger.gz |
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Project description:Tissue-resident memory T cells (TRM) have recently emerged as crucial cellular players for host defense in a wide variety of tissues and barrier sites. Insights into the maintenance and regulatory checkpoints of human TRM cells remain scarce, especially due to the difficulties associated with tracking T cells over time and spatially in humans. We therefore aimed to identify and characterize skin resident T cells in humans defined by their long-term in situ lodgement. Allogeneic hematopoietic stem cell transplantation paired with myeloablative chemotherapy unmasked long-term sequestration of host T cell subsets in the human skin despite complete donor T cell chimerism in the blood. Single-cell chimerism analysis paired with single-cell transcriptional profiling comprehensively characterized these bona fide long-term skin resident T cells and revealed differential tissue maintenance for distinct T cell subsets, specific TRM cell markers such as galectin-3, but also tissue exit potential with retention of the transcriptomic TRM cell identity. Analysis of 26 patients revealed profound interindividual variation in the tissue maintenance of host skin T cells and excluded a role for host T cells for the pathogenesis of chronic GvHD. Our data exemplify the power of exploiting a clinical situation as a proof-of-concept for the existence of bona fide human skin TRM cells and reveal long-term persistence of host immunity in the peripheral tissue but not in the circulation or bone marrow for a subset of patients.
2022-01-28 | GSE192590 | GEO
Project description:Background Immune tolerance and persistent mixed chimerism can be achieved reproducibly after combined organ and hematopoietic cell transplantation in mice conditioned with total lymphoid irradiation plus anti-thymocyte globulin. We studied the safety and reproducibility of this approach in a cohort of kidney transplant patients, and tried to identify immune monitoring procedures that can predict tolerance and guide complete immunosuppressive drug withdrawal. Methods Ten patients conditioned with 10 doses of total lymphoid irradiation and 5 doses of anti-thymocyte globulin were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA matched donors. Blood cell monitoring included changes in chimerism, balance of T cell subsets, gene expression, and responses to donor alloantigens. Results Nine of 10 patients developed multi-lineage chimerism without graft versus host disease (GVHD), and all had excellent graft function at the last observation point. Five of these with chimerism persisting for at least 12 months were completely withdrawn from immunosuppressive drugs for 6 to 35 months. Blood cells from patients off drugs showed development of specific unresponsiveness to donor alloantigens, M-bM-^@M-^\toleranceM-bM-^@M-^] profiles on gene microarrays, early high ratios of regulatory versus conventional naM-CM-/ve T cells, and early high levels of chimerism among NK cells. Conclusions Total lymphoid irradiation, and anti-thymocyte globulin promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and donor cell injections. Assays were identified that can assist in the safe withdrawal of immunosuppressive drugs. 45 Agilent Microarray samples were conducted, including 16 tolerance patients, 10 chronic rejection patients, 5 healthy normal controls, and 7 paired pre and post-transplant induced tolerance patients. The aim is to see whether induced tolerance patients show operational tolerance gene expression signature and can withdraw or minimize the immunosuppression regimens.
2012-12-15 | E-GEOD-17068 | biostudies-arrayexpress
Project description:Background Immune tolerance and persistent mixed chimerism can be achieved reproducibly after combined organ and hematopoietic cell transplantation in mice conditioned with total lymphoid irradiation plus anti-thymocyte globulin. We studied the safety and reproducibility of this approach in a cohort of kidney transplant patients, and tried to identify immune monitoring procedures that can predict tolerance and guide complete immunosuppressive drug withdrawal. Methods Ten patients conditioned with 10 doses of total lymphoid irradiation and 5 doses of anti-thymocyte globulin were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA matched donors. Blood cell monitoring included changes in chimerism, balance of T cell subsets, gene expression, and responses to donor alloantigens. Results Nine of 10 patients developed multi-lineage chimerism without graft versus host disease (GVHD), and all had excellent graft function at the last observation point. Five of these with chimerism persisting for at least 12 months were completely withdrawn from immunosuppressive drugs for 6 to 35 months. Blood cells from patients off drugs showed development of specific unresponsiveness to donor alloantigens, “tolerance” profiles on gene microarrays, early high ratios of regulatory versus conventional naïve T cells, and early high levels of chimerism among NK cells. Conclusions Total lymphoid irradiation, and anti-thymocyte globulin promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and donor cell injections. Assays were identified that can assist in the safe withdrawal of immunosuppressive drugs.
2012-12-15 | GSE17068 | GEO
Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD).
The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.
| 2381286 | ecrin-mdr-crc
Project description:Two independent ES cell lines (D4 and C2) were assessed for chimerism and germline transmission. Although these lines were able to produce chimerism at early passage, no germ line transmission was seen. After passaging in a proprietary medium and subcloning by detaching loosely connected cells and culturing in the recommended medium, both lines experienced an increase in potential as evidenced by an enhanced ability to go germ line. Analysis of early passage, and late passage detached and attached cells will allow the determination of genes that may be implicated in the increase of potential seen in these cells. Note: additional replicates may be added at a later date. Keywords: embryonic stem cells, chimerism, germline transmission
2006-01-24 | GSE4087 | GEO
Project description:Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival after kidney transplantation. We previously showed that tolerance could be induced and full donor chimerism, as well as immunosuppression withdrawal, was obtained in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx).
2018-05-07 | GSE106675 | GEO
Project description:Two independent ES cell lines (D4 and C2) were assessed for chimerism and germline transmission. Although these lines were able to produce chimerism at early passage, no germ line transmission was seen. After passaging in a proprietary medium and subcloning by detaching loosely connected cells and culturing in the recommended medium, both lines experienced an increase in potential as evidenced by an enhanced ability to go germ line. Analysis of early passage, and late passage detached and attached cells will allow the determination of genes that may be implicated in the increase of potential seen in these cells. Note: additional replicates may be added at a later date. Experiment Overall Design: this experiment include 6 samples and 34 replicates
2008-06-12 | E-GEOD-4087 | biostudies-arrayexpress
Project description:RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells.
PURPOSE: Phase I trial to study the effectiveness of treated donor stem cell transplantation in treating patients who have hematologic cancer.
| 2004049 | ecrin-mdr-crc
Project description:Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival after kidney transplantation. We previously showed that tolerance could be induced and full donor chimerism, as well as immunosuppression withdrawal, was obtained in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Gene expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection were compared. This dataset is part of the TransQST collection.
2018-05-07 | E-GEOD-106675 | biostudies-arrayexpress