Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.
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PMID:HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation. 196 10

Sixteen recipient-donor pairs who underwent unrelated BMT were analyzed for their HLA-class II identity by DNA-RFLP, in order to evaluate the importance of the genotypic HLA-DR, DQ, DP identity in the clinical outcome of unrelated bone marrow transplantation. From our study, a clear correlation between the HLA-DR, DQ, and DP genetic identity and acute GVHD (aGVHD) is not obvious since the number of studied cases is still limited. Nevertheless, it seems that the genetic identity influence the clinical outcome and patient survival. Six patients out of the ten who experienced severe aGVHD (greater than grade II) differed from their respective donors by HLA-DP mismatch in the GVH direction. Two patients rejected their grafts, and both presented HLA-DP incompatibilities in both GVH and HVG directions. Hence, HLA-DP may function as a transplantation antigen like the other HLA-class II molecules (DR, DQ) in unrelated BMT. Accordingly, we propose considering it in the pretransplantation histocompatibility testing. Nevertheless, further studies with larger numbers of cases should be done in order to confirm the role of HLA-DP. No correlation was observed between the mixed lymphocyte reaction (MLR) reactivity and the incidence of aGVHD. Accordingly, MLR response seems to be an incomplete indicator of GVHD, and a functional test is still to be found.
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PMID:HLA-DR, DQ, and/or DP genotypic mismatches between recipient-donor pairs in unrelated bone marrow transplantation and transplant clinical outcome. 197 52

HLA-DR expression by keratinocytes and enterocytes was studied in 23 patients undergoing BMT (12 autologous; 11 allogeneic). Two monoclonal antibodies were used to detect the HLA-DR antigen. Only in two patients before transplant and in one following autologous BMT was HLA-DR expressed on keratinocytes. Of 11 allogeneic recipients, 7 developed clinical GVHD, and HLA-DR-positive keratinocytes were seen in 6 of these. HLA-DR was expressed by enterocytes in 5 patients with GVHD and 4 of these also showed HLA-DR expression by keratinocytes. HLA-DR expression by keratinocytes correlated well with clinical GVHD. Expression of this antigen by enterocytes was associated with characteristic histological appearances of GVHD, even in the absence of intestinal symptoms. A combination of traditional and immunocytochemical techniques offers a sensitive and accurate method of confirming GVHD before it becomes florid.
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PMID:Class II antigen expression by keratinocytes and enterocytes--an early feature of graft-versus-host-disease. 245 41

Fifteen patients and their respective bone marrow donors were entered in this study 1 to 5 yr after allogeneic bone marrow transplantation. Peripheral blood E rosetting (T) cells were analyzed for their phenotypic characteristics as well as for their ability to regulate Ig synthesis in the in vitro PWM system. A close relationship was found between a high proportion of T8+/HNK-1+ cells and/or T8+/HLA-DR+ cells and a strong (greater than or equal to 50%) inhibition of the antibody response. It was noteworthy that even the patients without suppressor activity had high proportions of such cells when compared with normal marrow donors. Moreover, the suppression occurred irrespective of the presence or absence of chronic GVHD. Through negative selection experiments (with MAb and complement) and through immunofluorescence cell sorting, it was shown that the suppressor cells expressed the T8+, HNK-1+, HLA-DR- phenotype. They did not carry the Leu-11, NKH1A, or NKH2 determinants, which are expressed on mature functional NK cells. When examined by electron microscopy, they exhibited a morphology of resting agranular lymphocytes. The significant increase of these suppressor cells among the BMT patients was not correlated with clinical syndromes such as chronic GVHD or opportunistic viral infections, which argues against the notion of in vivo profound immunodeficiency coexisting with these cells.
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PMID:Persistence of T8+/HNK-1+ suppressor lymphocytes in the blood of long-term surviving patients after allogeneic bone marrow transplantation. 294 51

Low-density cells (LDC) prepared from peripheral blood by fractionation over hypertonic metrizamide contain 95% of cells with veiled morphology, almost all of which are HLA-DR-positive and have characteristics of antigen-presenting cells. In normal individuals the monoclonal antibodies RFD1 and RFD2 divide these cells into three phenotypically distinct populations, D1+D2-, D1-D2+ and D1-D2-. The RFD1-positive population is nonphagocytic. We have investigated the recovery of LDC in peripheral blood after (T cell-depleted) marrow transplantation, to assess whether defects in antigen-presenting cell (APC) subpopulations could contribute to the prolonged immune-paresis of marrow graft recipients. We find that APC of donor origin and with apparently normal morphology, phenotype, and function appear within 6 weeks of BMT. By three months the donor-derived nonphagocytic RFD1-positive subset has disappeared, although phagocytic RFD2-positive cells remain. The disappearance of the RFD1-positive subset is associated with a loss of antigen presentation by patients' LDC of the soluble protein antigen tetanus toxoid, though the capacity to present alloantigen and stimulate in a mixed lymphocyte reaction is retained. Donor-derived RFD1-positive cells and soluble antigen-presenting capacity do not reappear for one year or more. This biphasic recovery of RFD1-positive cells contrasted with the continued production of RFD2-positive APC, implies that the phenotypic and functional distinction between APC subpopulations in peripheral blood also reflects a separate ontogeny. Since these marrow graft recipients retain the phagocytic (RFD2-positive) APC but lose the nonphagocytic (RFD1-positive) APC subset, there is now an opportunity to explore the role of each subset in antigen processing and presentation.
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PMID:Differential recovery of phenotypically and functionally distinct circulating antigen-presenting cells after allogeneic marrow transplantation. 296 9

To analyze the mechanism of chronic graft-versus-host disease (GVHD) characteristic of autoimmune disease, we used a cell-mediated lympholysis assay to study the autoreactivity of PBL from two patients after MHC-matched BMT. Our data indicate the induction of CD3+CD4-CD8+ autoreactive cytotoxic T lymphocytes (CTL) in the one patient with chronic GVHD and an important role for allo-non-MHC (minor histocompatibility) antigen-specific CD3+CD4+CD8- helper T cells in this induction. Experiments using HLA-DR gene-transfected mouse L cells as target cells and blocking assays with anti-HLA class I and class II antibodies provided evidence that autoreactive CTL recognized HLA-DR antigen on autologous cells. Analysis of antigen-specific T cell proliferative responses in these patients to examine the effect of self HLA-DR-specific CTL on the antigen presenting cell (APC)-T cell interaction suggested that donor bone marrow-derived self HLA-DR-specific CTL are responsible for the decreased antigen-presenting ability of the patient's APC. These results suggest a new interpretation of the induction mechanism of chronic GVHD and its associated immunosuppression after MHC-matched BMT based on diminished APC function.
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PMID:Generation of self HLA-DR-specific CD3+CD4-CD8+ cytotoxic T cells in chronic graft-versus-host disease. 785 27

In order to discover some biological markers of acute graft-versus-host disease (aGVHD), we have studied the percentage of peripheral monocytes and T lymphocytes bearing HLA-DR and HLA-DQ class II molecules. This study included 25 allogeneic BMT in children, either with (n = 10) or without (n = 15) aGVHD. Within 2 months after transplantation, a higher percentage of DQ+ and DR+ monocytes and of DQ+ T lymphocytes was observed in patients without aGVHD compared with patients with aGVHD. The most discriminating marker was the strong increase in the percentage of DQ+ monocytes in patients without aGVHD (P = 0.001). In a sequential study, we observed a low percentage of DQ+ and DR+ peripheral blood mononuclear cells (PBMC) as long as the clinical manifestations of aGVHD continued. We speculate if the modulation of DQ and DR molecules on PBMC after BMT is a consequence of the action of some lymphokines, and if it plays a role in the regulation of the acute GVH reaction. We conclude that MHC class II molecules on peripheral mononuclear cells may be reliable biological markers for the diagnosis of aGVHD.
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PMID:A high percentage of HLA-DQ+ and HLA-DR+ mononuclear cells is associated with a low incidence of acute graft-versus-host disease after allogeneic bone marrow transplantation (BMT) in children. 818 44

Bone marrow transplant recipients have a functional T-cell deficit long after T-cell counts have returned to normal levels. Early after BMT, T-cell phenotype is predominantly CD45RO+/CD29high/HLA-DR+/CD38high. This profile is associated with activated memory cells in healthy subjects, but also appears on the earliest mature naive T-cells in times of lymphopoietic stress. Most of these cells apoptose in short-term unstimulated culture, suggesting that they would have had a similar fate in vivo. Twelve to 24 months after BMT, CD45RA+/CD29low/HLA-DR-/CD38low T cells increase, apoptosis decreases, and T-cell function normalizes. We hypothesize that in the adult, mature memory T cells regulate their own replacement by rescuing a proportion of newly generated naive cells from apoptosis. Ablation of memory cells consequent to high dose therapy disrupts this process, resulting in a protracted period of high lymphocyte turnover with few cells surviving to make the antigen-driven transition to memory cells. Infection with HIV-1 also eventuates in immune deficiency associated with a loss in CD4+ T cells and dominance of the phenotypic/apoptotic profile which we have associated with lymphopoietic stress. Recent data independently confirm that T-cell turnover is greatly elevated in HIV infection. Catastrophic or chronic depletion of memory T cells due to marrow ablative therapy or HIV-1 infection interferes with memory replacement, substituting short-lived hypofunctional naive T cells which characterize the state of immune amnesia.
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PMID:Lymphopoiesis, apoptosis, and immune amnesia. 859 62

The peripheral blood regeneration of natural killer (NK) cells was studied before and on 5 occasions during the first 6 weeks after autologous bone marrow transplantation (auto-BMT) in 10 patients with hematological malignancies and solid tumors. The number of NK cells (relative as well as absolute), enumerated by their lack of CD3 and their expression of CD56 recovered after a severe decline 1 week posttransplant to increase beyond pretransplantation levels during the next 2 weeks. Similar patterns were seen for the average NK activity against K562 as well as LAK cell lytic activity against Daudi but without the overshoot at weeks 2-3. Moreover, the fraction, but not the absolute numbers, of NK cells was found to correlate to the lytic NK activity. In contrast, no phenotypic marker was correlated to LAK activity. Immunophenotypic studies using three-color flow cytometry revealed that during the first 2 weeks after auto-BMT the phenotype of NK cells changed towards an immature phenotype (decreased CD45RA and CD11a) 1 week after transplant to an activated (increase in CD25, HLA-DR and CD11c) after 2-4 weeks. However, when the absolute number of selected phenotypically defined NK cell subsets(CD45RA, CD45RB, CD11a, CD11c, CD2, CD25, HLA-DR and fibronectin expressing CD56+,CD3- NK cells) were compared to the cytotoxic activity for each patient, we were not able to show any correlations except between the activation-related antigens CD25 and HLA-DR on the one hand, and NK lysis on the other, and only 3 weeks after auto-BMT. We conclude that NK cell function recovers quickly following auto-BMT concomitantly with the emergence of a transiently altered phenotype which increased expression of activation-related antigens.
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PMID:Natural killer cells in peripheral blood after autologous bone marrow transplantation: a combined phenotypic and functional study. 883

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.
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PMID:Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes. 1116 18


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