PIGA mutations in recipients following alemtuzumab-based T-cell depleted alloSCT
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PROVIDER: PRJEB24004 | ENA |
REPOSITORIES: ENA
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Project description:PIGA mutations in T-cell clones isolated from recipients who received alemtuzumab-based T-cell depleted allogeneic stem cell transplantation and from a healthy donor
| PRJEB24004 | ENA
Project description:Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 M-bM-^@M-^S 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- M-NM-3 and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction. B6 recipients were irradiated with 10.0 Gray, administered from a 137 Cs source. Splenocytes from C3H mice were prepared as single cell suspensions in PBS, depleted of red blood cells and counted. 2 M-bM-^@M-^S 3 M-CM-^W 10^7 C3H splenocytes in a volume of 200 M-NM-<l were transplanted into B6 recipients via tail vein injection (4 mice per group per experiment) 4 M-bM-^@M-^S 6 h after irradiation. Mice in the treatment group with anti-ICOSL mAb and their respective controls, received 500 M-NM-<g mAb i. p starting at day 0 or day 3, followed by subsequent injections of 200 M-NM-<g of mAb every other day. At day 4 after transplantation RNA of spleen cells was prepared and subjected to microarray analysis. Combined RNA from allogeneic transplanted mice was hybridized onto 2 independent arrays.
2009-09-14 | E-GEOD-17995 | biostudies-arrayexpress
Project description:Approximately 2% of heathy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. We examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and hepatectomy patients and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 hepatectomy patients who received care at the Kyusyu University Hospital between May 1997 and September 2017. Total RNA was extracted from peripheral blood samples of patients/recipients collected postoperatively. HPgV RNA was measured using real-time polymerase chain reaction (RT-PCR). Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and two patients (1.1%) had HPgV viremia. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion as HPgV RNA was detected from the blood bag transfused to the recipient during LT. Additionally, HPgV infection induced the upregulation of interferon stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs). LT recipients had higher HPgV viremia compared to hepatectomy patients. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients.
2019-07-28 | GSE131504 | GEO
Project description:The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T‐cells. To this end, we tracked αβT‐cell clones during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and during immune reconstitution after transfer to transplant recipients. More than 250 αβT‐cell clones were tracked from donor to recipient. These clones consisted almost exclusively of CD8+ effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clones could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clones after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.
2023-01-27 | GSE222633 | GEO
Project description:Reactivation of latent HCMV is a significant infectious complication of organ transplantation, and current therapies target viral replication once reactivation of transcriptionally silent, latent virus has already occurred. The specific molecular pathways that activate viral gene expression are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. MCMV is a valuable model for studying latency and reactivation of CMV induced by organ transplantation. We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces transcriptional reactivation of immediate early (IE) gene expression within 48 hr. We used microarrays to profile global mouse kidney gene expression associated with transcriptional reactivation of MCMV immediate early gene expression at 48 hr after transplant of MCMV latently infected kidneys into allogeneic recipients. We identified differentially expressed genes and pathways associated with both early acute rejection and reactivation of MCMV. control vs. allograft
2015-08-27 | E-GEOD-72392 | biostudies-arrayexpress
Project description:Identification of tongue microbiota of allogeneic hematopoietic stem cell transplantation recipients
| PRJDB9265 | ENA
Project description:In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. The complete database comprised the expression measurements of 48766 probes in liver biopsies. The liver biopsy specimens available for the study were obtained: a) before immunosuppressive drugs were discontinued from tolerant (TOL, n=24) and non-tolerant (Non-TOL, n=29) recipients; b) at the time of rejection from non-tolerant recipients (Non TOL REJ, n=18); In addition, liver tissue samples were also collected from the following control patient groups: a) liver transplant recipients with chronic hepatitis due to recurrent hepatitis C virus infection (HEPC, n=12); b) liver transplant recipients with typical acute cellular rejection taking place during the immediate post-transplant period (REJ, n=9); c) liver transplant recipients under maintenance immunosuppression with normal liver function and normal liver histology 1 year after transplantation (CONT-Tx, n=8); and d) non-transplanted patients undergoing surgery for colorectal liver metastases (CONT, n=10).
2012-01-09 | E-GEOD-26625 | biostudies-arrayexpress
Project description:The goal of this study is to determine if pDCs reconstituted from T cell depleted allogeneic STAT1-/- bone marrow express genes that contribute to Graft versus host disease (GVHD) resistance as compared to STAT1+/+ bone marrow
2014-07-25 | GSE59731 | GEO
Project description:Analysis of donor CD4+ and CD8+ T cells purified from spleens and ovaries after murine syngeneic and allogeneic hematopoietic stem cell transplantation Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). While the role of pretransplant conditioning regimen has been well appreciated, increasing application of reduced-intensity conditioning facilitated us to revisit the other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. To study transcriptomes of donor T cells infiltrating into the ovary, donor T cells were sorted from recipients' ovaries and microarray analysis was performed.
2017-05-12 | GSE81397 | GEO
Project description:The goal is to identify molecules involved in the accumulation of blood MDSCs in tolerant kidney allografted recipients when compared to syngeneic grafted recipients. In this study 27,088 individual rat genes expression from total mRNA of blood MDSCs from 3 tolerated allogeneic kidney transplanted recipient by anti-CD28, were compared to MDSCs from 3 syngeneic kidney transplanted recipient at day 100 post transplantation.
2011-04-13 | E-GEOD-28545 | biostudies-arrayexpress