FcgRIIB+ and FcgRIIB- OT-I T cells d14 post OVA skin graft
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118439 | GEO | 2019/12/27
REPOSITORIES: GEO
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Project description:FcgRIIB+ and FcgRIIB- OT-I T cells d14 post OVA skin graft
| PRJNA485651 | ENA
Project description:Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call “defensive tolerance.” This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.
2024-06-20 | GSE252337 | GEO
Project description:Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Recent data demonstrate that non-self recognition by graft infiltrating macrophages initiates transplant rejection. Using an experimental transplantation mouse model, we isolated graft-infiltrating macrophages from two transplantation settings: untreated rejecting mice and treated with mTORi-HDL nanobiologics. We used microarrays to detail the global programme of gene expression underlying macrophage dependent organ transplant rejection and identified distinct classes of up-regulated genes during this process, which are down-regulated following tolerogenic treatment with mTORi-HDL nanobiologics.
2018-10-31 | GSE119370 | GEO
Project description:Purpose: The molecular circuits which govern CD8 T cell fate after alloimmunization by transplantation or pregnancy are unknown. The goals of this study are to perform whole transcriptome profiling (RNA-seq) of antigen-experienced CD8 T cells in parous and grafted mice to determine whether these cells become memory or exhausted T cells. Methods: mRNA profiles of OT-1 T cells recovered fom naive,OVA-skin grafted and OVA-parous mice were generated by bulk RNA-sequencing. OT-1 cells were FACS sorted from 10 individual mice per each of the three groups and then pooled together into three replicate samples per group. The sequence reads that passed quality filters were analyzed after aligning (STAR) with EdgeR. Results: Comparison of OT-1 T cells from OVA-grafted and OVA-parous mice revealed 400 differentially expressed genes. Conclusions: Skin grafting promotes the differentiation of canonical memory CD8 T cells whereas pregnancy promotes the differentiation of exhausted CD8 T cells with diminished recall capacity.
2021-12-06 | GSE188808 | GEO
Project description:Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. We utilized TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following ICI therapy. ICI therapy was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, many of which were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.
2023-02-01 | GSE216762 | GEO
Project description:Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. We utilized TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following ICI therapy. ICI therapy was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, many of which were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.
2023-02-01 | GSE216758 | GEO
Project description:Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. We utilized TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following ICI therapy. ICI therapy was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, many of which were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.
2023-02-01 | GSE216756 | GEO
Project description:In this study we employed transcriptome mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response. The flow cytometry data confirms depletion of specific cell subsets in response to ATG induction and immunosuppression with sustained decreases in CD4 as well as CD8 cell subsets. A series of T cell activation markers were expressed from Pre-Tx to 12 weeks indicating the evolution of immunity including expansion of CD45RO+CD62L- effector memory cells. Serial whole blood transcript monitoring demonstrated over 2000 differentially expressed genes, with over 80 percent down-regulated Post-Tx. However, cell subset analysis revealed a unique spectrum of subset-specific gene expression with time-dependent changes, with contrasting significant Post-Tx gene upregulation. Our results provide a unique view of the complex evolution of immune/inflammatory molecular networks marking the early post transplant immune response. A critical finding is that analysis of the constituent blood cell subsets provides an entirely new level of detail revealing the nature of this process, effectively deconvoluting the changes that are otherwise lost in the noise of cellular complexity of whole blood. Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, cell subsets, flow cytometry, serial monitoring We employed Affymetrix HG-U133 Plus 2.0 GeneChips for mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response.
2010-11-01 | E-GEOD-24223 | biostudies-arrayexpress
Project description:Acute rejection episodes trigger chronic renal allograft vasculopathy. Numerous leukocytes, predominantly monocytes, accumulate in graft blood vessels during reversible acute rejection preceding chronic rejection of rat kidneys. We speculate that they contribute to transplant vasculopathy and set out to characterize them. Allogeneic renal transplantation was performed in the Fischer 344 to Lewis rat strain combination, Lewis isografts served as controls. Leukocytes were harvested by intensive perfusion of graft blood vessels and subjected to flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Kidneys of LEW and F344 rats were transplanted in LEW rats. Five biological replicates were performed for both isogenic and allogenic transplantation. Transcriptomes of allogenics were compared to isogenics on 5 dual-color hybridizations.
2010-09-24 | E-GEOD-18266 | biostudies-arrayexpress
Project description:Acute rejection episodes trigger chronic renal allograft vasculopathy. Numerous leukocytes, predominantly monocytes, accumulate in graft blood vessels during reversible acute rejection preceding chronic rejection of rat kidneys. We speculate that they contribute to transplant vasculopathy and set out to characterize them. Allogeneic renal transplantation was performed in the Fischer 344 to Lewis rat strain combination, Lewis isografts served as controls. Leukocytes were harvested by intensive perfusion of graft blood vessels and subjected to flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling.
2010-09-24 | GSE18266 | GEO