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Hematopoietic Chimerism (hematopoietic + chimerism)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Hematopoietic Chimerism

  • mixed hematopoietic chimerism
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    Selected Abstracts

    Immunomodulatory Effects of Mixed Hematopoietic Chimerism: Immune Tolerance in Canine Model of Lung Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
    R. A. Nash
    Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n = 5) vs. nonchimeric (n = 7) recipients (p , 0.05, Fisher's test). There were histological changes consistent with low-grade rejection in 3/5 of the lung grafts in chimeric recipients at ,1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INF,+, CD4+IL-4+ and CD8+ INF,+ T-cell subsets in the blood (p < 0.0001 for each of the three T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGF, were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response. [source]

    Capillary electrophoresis for chimerism monitoring by PCR amplification of microsatellite markers after allogeneic hematopoietic cell transplantation

    CLINICAL TRANSPLANTATION, Issue 3 2005
    Alexandros Spyridonidis
    Abstract:, Background:, Hematopoietic chimerism has been demonstrated to be relevant for donor cell engraftment and detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). In the light of increasing numbers of non-myeloablative aHCT as a treatment modality sensitive, rapid, and accurate chimerism monitoring techniques acquire novel relevance. Methods:, We evaluated the informativeness of five microsatellite markers in 376 donor/recipient pairs and evaluated the ability of capillary electrophoresis to detect mixed chimerism after aHCT. The sensitivity for capillary electrophoresis with respect to different markers was determined by limiting dilution assays with mixed chimerism samples containing defined amounts of cells or DNA. Furthermore, capillary electrophoresis was applied in 17 retrospectively selected patients with a mixed chimerism detected previously by gel electrophoresis, having undergone aHCT for different hematologic diseases and initially achieving a complete donor chimerism. Results:, In 163 of 165 (98%) of all related and 210 of 211 (99%) unrelated transplants the microsatellites identified informative alleles. The sensitivity and accuracy was higher with capillary electrophoresis when compared with gel electrophoresis with three of five microsatellites. Potential pitfalls with the application of capillary electrophoresis was preferential amplification and the occurrence of stutter peaks in the representative area. Investigation of the selected patient samples demonstrated that detection of a mixed chimerism was earlier with capillary electrophoresis when compared with gel electrophoresis. The detected recipient genotype by capillary electrophoresis examination, despite a negative gel electrophoresis result, ranged from 0.7 to 7.1%. Conclusions:, We conclude that chimerism assessment with our five microsatellites identified informative alleles in 99% of all donor/recipient pairs and may therefore be of use when establishing an institutional chimerism testing procedure. Capillary electrophoresis displayed a high sensitivity and accuracy for detecting a mixed chimerism in vitro and in vivo. [source]

    Immunomodulatory Effects of Mixed Hematopoietic Chimerism: Immune Tolerance in Canine Model of Lung Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
    R. A. Nash
    Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n = 5) vs. nonchimeric (n = 7) recipients (p , 0.05, Fisher's test). There were histological changes consistent with low-grade rejection in 3/5 of the lung grafts in chimeric recipients at ,1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INF,+, CD4+IL-4+ and CD8+ INF,+ T-cell subsets in the blood (p < 0.0001 for each of the three T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGF, were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response. [source]

    NK Cells Mediate Costimulation Blockade-Resistant Rejection of Allogeneic Stem Cells During Nonmyeloablative Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2006
    L. S. Kean
    Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 × 108/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation. [source]

    Allogeneic Parenchymal and Hematopoietic Tissues Differ in Their Ability to Induce Deletion of Donor-Reactive T Cells

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2003
    Thomas R. Jones
    The establishment of immune tolerance to self antigen expressed exclusively in the periphery is a crucial yet incompletely understood feature of the immune system. A dominant concept of peripheral tolerance has been that exposure of T cells to signal one, the TCR,MHC interaction, in the absence of signal two, or costimulation, is a major mechanism of peripheral tolerance. This model suggests that any cell type that expresses MHC-peptide complexes, be they of self or foreign origin, should have the capacity to tolerize antigen-specific T cells when critical costimulatory interactions are interrupted. However, a spectrum of responses, from permanent engraftment to rapid rejection, has been observed in various transplantation models utilizing costimulatory blockade. Therefore we undertook a series experiments to directly assess the tolerogenic potential of donor hematopoietic and parenchymal cells. We find that allogeneic tissues differ profoundly in their ability to promote peripheral tolerance concurrent with combined blockade of B7-CD28 and CD40-CD40L pathways. Non-vascularized and vascularized parenchymal grafts as well as donor-specific transfusions promote varying degrees of donor-specific hyporesponsiveness, but fail to induce donor-reactive T-cell deletion; whereas establishment of stable hematopoietic chimerism promotes specific tolerance mediated by deletion of donor-reactive cells in the periphery. [source]

    Comments on ,Skin transplantation to monitor clinical donor-related tolerance in mixed hematopoietic chimerism' by Mache et al. (Pediatr Transplant 2006;10:128,131)

    PEDIATRIC TRANSPLANTATION, Issue 6 2006
    Christian Urban
    No abstract is available for this article. [source]