Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood lymphocyte subsets were enumerated at regular intervals during the first year after allogeneic bone marrow transplantation (BMT) in 21 Chinese patients. Eight of these patients had acute graft-versus-host disease (GVHD) while they were assessed at the time of engraftment. Our results show in patients receiving allogeneic BMT: (1) T and NK cells were the predominant lymphocyte subsets in the early reconstitution stage while B cells were severely depleted; (2) absolute numbers of the major lymphocyte subsets normalised in 4-5 months; (3) an increased percentage of T cells that expressed the activation antigen HLA-DR and a reversed CD4:CD8 ratio were observed throughout the first 12 months after BMT; (4) patients with acute GVHD had significantly higher white cell count and NK cell percentage than those not complicated by acute GVHD.
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PMID:Peripheral blood lymphocyte subsets after allogeneic bone marrow transplantation: reconstitution and correlation with the occurrence of acute graft-versus-host disease. 761 4

To determine whether administration of G-CSF induces phenotypic or functional changes in T cells, we examined peripheral blood T cells from normal individuals receiving G-CSF for activation antigen and adhesion molecule expression before and after G-CSF administration. G-CSF (10 microg/kg/day) was administered subcutaneously to 14 normal individuals for 3-5 days and their PBMC were serially analyzed with monoclonal Ab (mAb) directed to HLA-DR, CD45RO, CD45RA, CD25, CD122, CD95, CD11a, CD49d, CD44 and CD62L (L-selectin) coupled with anti-CD3 mAb. Among T cells positive for these antigens, only the proportion of T cells expressing L-selectin significantly decreased from 68% to 37% after 3-day G-CSF administration. When peripheral blood CD3+ T cells obtained before and after G-CSF administration were sorted into two populations depending on the expression of L-selectin and tested for their proliferative response to allogeneic B cells, the reactivity of L-selectin- cells to alloantigen stimulation was consistently lower than that of L-selectin+ cells regardless of the exposure to G-CSF. The decrease in the relative number of L-selectin+ cells induced by G-CSF administration may contribute to the unexpectedly low incidence of severe acute GVHD after allogeneic PBSC transplantation.
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PMID:Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in the peripheral blood that respond better to alloantigen stimulation than L-selectin- T cells. 1019 95

Graft-versus-host disease (GvHD) is a multistep immune process involving lymphocyte activation, proliferation and target cell killing. We have devised a novel method for the selective depletion of alloreactive cells from haematopoietic stem cell grafts which retains a pool of immunocompetent lymphocytes possessing antiviral activity with the potential to hasten immune reconstitution. The method is based upon the expression of the activation antigen CD69 on responding donor lymphocytes in a cytokine-modified mixed lymphocyte culture (mMLC) and depletion of these cells by paramagnetic bead sorting. We have previously demonstrated the in vitro efficacy of this system for the removal of alloreactive cells in both human leucocyte antigen-mismatched and -matched settings. Here, we describe a non-obese diabetic/severe combined immunodeficient murine model of aggressive GvHD in which we have tested its in vivo efficacy. Murine recipients of infusions of non-manipulated major histocompatibility complex class I and class II mismatched donor T cells suffered rapid onset of acute, and generally fatal, GvHD. This model is akin to aggressive clinical transfusion-related GvHD. Recipients of lymphocyte infusions depleted of CD69+ alloreactive donor cells ex vivo and monitored for 10 weeks post infusion demonstrated significantly improved survival (71.4% compared with 12.5% in the non-manipulated group) and the absence of clinical GvHD despite the presence of circulating donor lymphocytes.
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PMID:Alloantigen-specific T-cell depletion in a major histocompatibility complex fully mismatched murine model provides effective graft-versus-host disease prophylaxis in the presence of lymphoid engraftment. 1210 Jan 33

Allogeneic hematopoietic stem cell transplantation is the treatment of choice for many hematological malignancies. Its efficacy is limited by graft-versus-host disease (GVHD), the leading cause of post-transplant morbidity and mortality. GVHD is mediated by a subpopulation of T cells in the stem cell graft. Ex vivo T cell depletion of all T cells of the graft can prevent development of GVHD but can lead to a delay in immune reconstitution and an increase of potentially lethal opportunistic infections and leukemic relapses. Hypothetically, an approach that enables a selective depletion of the alloreactive donor T cells that cause GVHD while preserving third party (anti-leukemic and anti-microbial) reactivity would be optimal for recipients of HSCT. Our preliminary data demonstrated that an anti-CD25 immunotoxin, which reacts with a cell surface activation antigen, can selectively deplete alloreactive donor T cells activated by non-leukemic recipient white blood cells while preserving the beneficial third-party reactivity in vitro. In this report we describe a method for clinical-scale ex vivo selective depletion of alloreactive donor T cells using the anti-CD25 immunotoxin, RFT5-SMPT-dgRTA. Two logs of alloreactive T cells could be selectively depleted while preserving third party reactivity. This method was reproducible in 10 pre-clinical experiments with 8 HLA-mismatched healthy volunteer pairs and 2 HLA-matched sibling donor/patient pairs.
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PMID:Clinical-scale selective depletion of alloreactive T cells using an anti-CD25 immunotoxin. 1293 44

Eliminating alloreactive cells from T-cell populations would enable the transfer of immune function to patients who receive stem cell transplants. However, high-efficiency depletion has proved difficult to achieve. We sought to develop ex vivo approaches for the maximal depletion of alloreactive CD4(+) T cells. Using a flow cytometric cell sorting approach after mixed lymphocyte reaction (MLR) culture, we have found that sorted CFSE(bright) (5-(and-6)-carboxyfluorescein diacetate succinmidyl ester) (nondivided) and activation antigen-negative cells are markedly depleted of alloreactivity. With HLA-mismatched peripheral blood mononuclear cell (PBMC) stimulators we have consistently attained (90%-95%) depletion of alloreactivity. Importantly, when purified matured monocyte-derived dendritic cells (DCs) are used as stimulators, a 100-fold (99%) reduction in alloreactivity was attained, resulting in abrogation of the secondary MLR. Significantly, the CFSE(bright) CD25(-) cells recovered from these cultures retained general immunoreactivity, including responses to Candida and cytomegalovirus (CMV) antigens. In addition, a CFSE-based approach was tested and found to be sufficient for graft-versus-host disease (GVHD) prevention in vivo, in a major histocompatibility complex (MHC) class II disparate murine model. This efficient approach to selectively deplete mature alloantigen-specific T cells may permit enhanced immune reconstitution without GVHD.
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PMID:Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation. 1452 83

Selective depletion of alloreactive T cells from stem-cell allografts should abrogate graft-versus-host disease while preserving beneficial T cell specificities to facilitate engraftment and immune reconstitution. We therefore explored a refined immunomagnetic separation strategy to effectively deplete alloreactive donor lymphocytes expressing the activation antigen CD69 upon stimulation, and examined the retainment of antiviral, antileukemic, and immunoregulatory T cells. In addition to the CD69high T cell fraction, our studies retrieved two T cell subsets based on residual CD69 expression. Whereas, truly CD69(neg) cells were devoid of detectable alloresponses to original stimulators, CD69-low (CD69low)-expressing T cells elicited significant residual alloreactivity upon restimulation. In interferon-gamma enzyme linked immunospot assays, anti-cytomegalovirus and anti-Epstein-Barr virus responses were preserved at significant numbers among CD69neg T lymphocytes. Accordingly, T cells recognizing the leukemia-associated Wilm's tumor-1 antigen were still detectable in the CD69neg subset. However, antiviral and antileukemic specificities were also consistently found within CD69low T cells, suggesting that memory-type donor T cells were partially captured due to residual CD69 expression. Finally, CD4+CD25+ Foxp3+ immunoregulatory T cells did not upregulate CD69 upon allogeneic stimulation. Our data suggest that CD69-mediated removal of alloreactivity can result in efficient allodepletion, but may partially affect the persistence of antiviral and antileukemic donor memory specificities captured among CD69low-expressing lymphocytes.
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PMID:Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. 1632 14

Human umbilical cord blood derived stromal cells (hUCBDSCs), a novel resource isolated by our laboratory, have been shown to exert an immunologic regulation. Very late activation antigen-4 (VLA-4) has been associated with graft-versus-host disease (GVHD). This study aimed to investigate the possible mechanism by in vitro co-cultured splenocytes of donor mice with hUCBDSCs and in haploidentical stem cell transplantation in mice with acute GVHD. Both hUCBDSCs and human bone marrow stromal cells (hBMSCs) elicited decreased lymphocyte expression of VLA-4, but this decrease was stronger with hUCBDSCs than with hBMSCs (p<0.05). Cotransplantation of bone marrow with hUCBDSCs significantly decreased the expression of VLA-4 compared with control mice (p<0.05). A significant reduction of VLA-4 labeling in the target organs of GVHD was evident in haploidentical mice cotransplanted with hUCBDSCs. Our study shows that hUCBDSCs may protect mouse recipients of haploidentical stem cell transplantation from aGVHD via downregulating the expression of VLA-4.
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PMID:Regulation of acute graft-versus-host disease by human umbilical cord blood derived stromal cells in haploidentical stem cell transplantation in mice through very late activation antigen-4. 2131 Jun 63