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)

Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease after CB transplantation. Here, CBDC were identified as a HLA-DR+ cell population, lacking the CD3, CD11b, CD14, CD16, CD19, CD34, CD56, and glycophorin A lineage markers (lin). This lin-/HLA-DR+ population represented 0.3% +/- 0.1% (mean +/- SD; range, 0.1% to 0. 6%; n = 15) of CB mononuclear cells, and CB contained 5.4 +/- 3.2 x 10(3) CBDC/mL (1.8 to 13.0 x 10(3); n = 15). CBDC expressed CD4, CD11a, CD18, CD45RA, CD50, CD54, and CD123, but showed no expression of CD1a, CD11c, CD33, CD40, CD45R0, CD80, CD83, and CD86 and only limited expression of CD58, CD102, and CD116. Despite this immature phenotype, immunomagnetically lin--enriched CBDC were potent stimulators of allogeneic CB T cells. As few as 266 +/- 107 (193 to 530; n = 10) lin-/HLA-DR+ CBDC stimulated a significant response. However, CBDC failed to take up protein or peptide antigens. Thus, in CB there is a prevalence of a DC subpopulation, resembling the CD11c- DC identified in tonsils, the so-called plasmacytoid T cells, which may exert a function distinct from the CD11c+ DC subpopulation.
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PMID:Identification of cord blood dendritic cells as an immature CD11c- population. 1009 Sep 40

Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1 beta and TNF-alpha produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64(+)monocytes producing intracellular IL-1 beta and TNF-alpha was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64(+)CD14(+)) was different to that of AB monocytes (CD64(+)CD14(+), CD64(+)CD33(+) and CD64(+) CD45RO(+)). These results suggest that the lower capacity of CB monocyte populations to produce IL-1 beta and TNF-alpha might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes.
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PMID:Intracellular cytokine profile of cord and adult blood monocytes. 1143 25

A 2-year-old Japanese boy who presented with multiple cervical, axillary, and inguinal lymphadenopathy was diagnosed by immunocytochemical analysis as having myeloid/natural killer (NK) cell precursor acute leukemia. Leukemic blasts in the bone marrow were positive for CD56 (NK marker), CD7 (T-cell marker), CD33 (myeloid marker), CD34, and HLA-DR. Tumor cells in a lymph node were also positive for CD2, cytoplasmic CD3 (T-cell marker), CD7, CD33, CD34, and CD56, but negative for peroxidase staining and other T-cell, NK, and myeloid markers. Southern blot analysis showed no rearrangement bands for T-cell receptor delta and immunoglobulin heavy chain. Chromosomal analysis revealed 46,XY,inv(7)(p21q21). Neither chemotherapy for acute lymphoblastic leukemia nor that for acute myeloid leukemia induced remission in this patient. However, complete remission was achieved by the administration of L-asparaginase (6,000 U/m2 for 5 days). Because the disease was considered refractory to standard chemotherapy, cord blood transplantation was performed from an HLA 1-locus mis-matched unrelated donor. The conditioning regimen consisted of total body irradiation, cytarabine, and cyclophosphamide, and cyclosporine and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Hematological reconstitution was rapid, and only grade I acute GVHD was observed. The patient has been in remission for more than 24 months after transplantation. Our findings indicate that combination therapy with L-asparaginase and allogeneic stem cell transplantation may be useful for the treatment of myeloid/NK cell precursor acute leukemia.
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PMID:Treatment of a child with myeloid/NK cell precursor acute leukemia with L-asparaginase and unrelated cord blood transplantation. 1193 70

Stem cell-dose escalation is one way to overcome immune rejection of incompatible stem cells. However, the number of hematopoietic precursors required for overcoming the immune barrier in recipients pretreated with sublethal regimens cannot be attained with the state-of-the-art technology for stem cell mobilization. This issue was addressed by the observation that cells within the human CD34(+) population are endowed with veto activity. In the current study, we demonstrated that it is possible to harvest about 28- to 80-fold more veto cells on culturing of purified CD34(+) cells for 7 to 12 days with an early-acting cytokine mixture including Flt3-ligand, stem cell factor, and thrombopoietin. Analysis of the expanded cells with fluorescence-activated cell-sorter scanning revealed that the predominant phenotype of CD34(+)CD33(-) cells used at the initiation of the culture was replaced at the end of the culture by cells expressing early myeloid phenotypes such as CD34(+)CD33(+) and CD34(-)CD33(+). These maturation events were associated with a significant gain in veto activity as exemplified by the minimal ratio of veto to effector cells at which significant veto activity was detected. Thus, whereas purified unexpanded CD34(+) cells exhibited veto activity at a veto-to-effector cell ratio of 0.5, the expanded cells attained an equivalent activity at a ratio of 0.125. The availability of novel sources of veto cells such as those in this study might contribute to the realization of immunologic tolerance in "minitransplants," without any risk of graft-versus-host disease.
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PMID:Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34(+) cells. 1201 Aug 23

This article describes a rare case of bone marrow transplantation (BMT) from an unrelated donor (URD) in an adult Japanese male with Down syndrome (DS) diagnosed as having acute mixed lineage leukemia. Examination of peripheral blood demonstrated WBC 6.2 x 10(9)/l with 45.5% blasts at admission. Leukemic blasts with positive peroxidase stain, but negative periodic acid-Schiff stain comprised 91.6% on bone marrow specimen. Surface marker analysis of these blasts showed the following: CD3(-), CD5(-), CD7(-), CD10(+), CD19(+), CD13(+), CD14(-), CD33(+), CD34(+), CD41a(-), and CD56(-). Based on these data, he was diagnosed as having acute mixed lineage (myeloid and B-lymphoid lineage) leukemia. He achieved complete remission (CR) by lymphoid-oriented chemotherapy performed after ineffective myeloid-oriented therapy. After four courses of consolidation chemotherapy for lymphoid lineage blasts, recurrence due to proliferation of myeloblasts had occurred. Thereafter, a second CR was obtained by low dose cytosine arabinoside (AraC) therapy. As this patient was considered to have a high risk of relapse, we selected allogeneic BMT from URD. Severe stomatitis due to methotrexate (MTX) occurred probably due to altered pharmacokinetics usually observed in DS patients. Though acute graft-versus-host disease (GVHD) of systemic skin (grade II) and pneumonia were observed during neutropenia due to the post-conditioning regimen, he could be discharged from our hospital on the 135th day after BMT. On day 205 post-BMT, however, bronchiolitis obliterans (BO) occurred as a chronic GVHD disorder. Despite therapy with prednisolone and FK506, he died on day 400 post-BMT because of respiratory failure due to BO. In DS patients, superfluous toxicities due to MTX and AraC treatment have been reported, and these toxicities have been considered due to altered pharmacokinetics in patients with DS. This patient could tolerate the transplant conditioning regimen commonly used in patients without DS.
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PMID:Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome. 1270 27

Studies in mice and humans demonstrate that transplantation of hematopoietic progenitors in numbers larger than commonly used ("megadose" transplants) overcomes major genetic barriers. In vitro studies suggest that veto cells, within the population of hematopoietic progenitors, facilitate this favorable outcome. Thus, when purified CD34(+) cells were added to bulk mixed-lymphocyte reactions (MLRs) they suppressed CTLs against the donor's stimulators, but not against stimulators from a third party. This tolerizing activity depends on cell contact and can be blocked by the caspase inhibitor BD-FMK, suggesting that the effector host T cells are deleted by apoptosis upon interaction with the CD34(+) cells. Early myeloid CD33(+) cells generated by short-term ex vivo expansion of CD34(+) cells also exhibit veto activity, and these cells can be grown in large numbers. Tolerance induction can be further enhanced by other veto cells. Perhaps the most potent veto cell is the CD8+ CTL. However, this cell is also associated with marked GVHD (graft-versus-host disease. GVHD can be separated from the veto activity by generating anti-third party CTLs under IL2 deprivation. Under such selective pressure only the stimulated clones which make IL2 can survive, while anti-host clones die. In vivo studies show that such anti-third party veto CTLs can be used safely for tolerance induction without GVHD.
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PMID:Hematopoietic stem cell transplantation across major genetic barriers: tolerance induction by megadose CD34 cells and other veto cells. 1279 85

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.
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PMID:Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation. 1290 Jul 75

This study aimed to identify which graft product subset of CD34+ cells might be the most predictive of early hematopoietic recovery following allogeneic peripheral SCT (allo-PBSCT). The relationship between the number of 'mature' subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD133-) and 'immature' subsets of CD34+ cells (CD34+/CD33-, CD34+/CD38-, CD34+/DR- and CD34+/CD133+) and early neutrophil and platelet engraftment were studied in a homogeneous series (for disease, pre transplant chemotherapy, conditioning regimen and GVHD prophylaxis) of 30 AML patients after allo-PBSCT from HLA-identical siblings. In our experience, the total CD34+/CD133+ cell number was inversely correlated with the days required for the recovery of 0.5 x 10(9)/l neutrophils (r=or-0.82, P=0.02) and platelets of 20 x 10(9)/l (r=or-0.60, P=0.06); this correlation was better than the total CD34+ cell dose and neutrophil (r=or-0.70, P=0.04) and platelet engraftment (r=or-0.56, P=0.07). We suggest that a high number of CD34+/CD133+ PBSC may be associated with faster neutrophil and platelet recovery; these findings may help to predict the repopulating capacity of PBSC in patients after allo-PBSCT, especially when a relatively low number of CD34+ cells is infused.
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PMID:Subsets of CD34+ and early engraftment kinetics in allogeneic peripheral SCT for AML. 1842 47

This study was purposed to explore the immunoregulatory effects of human bone marrow mesenchymal stem cells (MSCs) on active T lymphocytes in vitro and the new strategy to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononuclear cells from human peripheral blood cells were isolated and cultured in the presence of phytohemagglutinin (PHA) (final concentration was 10 microg/ml) for different times. The ability of T lymphocyte proliferation and activation was measured by (3)H-Thyramine incorporation. The expressions of CD3(+)CD4(+), CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) on T cells were detected by FCM after coculture for 72 hours. Experiment was divided into 4 groups: A group as control (no added MSCs), B group (actived T cells + 2 x 10(4) MSCs), C group (actived T cells + 4 x 10(4) MSCs), D group (actived T cells + 8 x 10(4) MSCs). The results showed that the ability of T lymphocyte proliferation in the same PHA concentration increased with prolonging of time. ability of T lymphocyte proliferation was strongest when culturing for 48 hours (p < 0.01); the expressions of CD44, CD105, CD29 and FIK1 of MSCs were positive, expressions of CD33, CD34, CD45 and HLA-DR were negative. MSCs inhibited T lymphocyte proliferation and the inhibitory effect depended on the amount of MSCs. CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) T cells cocultured with MSCs increased obviously and CD3(+)CD4(+) expression significantly decreased, as compared with control group (p < 0.01). It is concluded that the MSCs inhibit T lymphocyte proliferation induced by mitogen (PHA), and perform their immunosuppressive function by up-regulation of CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) expressions and down-regulation of CD3(+)CD4(+) expression.
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PMID:[Immunoregulatory effect of mesenchymal stem cells on active T lymphocytes]. 1892 8

We report 2 patients with plasmacytoid dendritic cell leukemia (pDCL) expressing CD4, CD56, CD33, CD36, HLA-DR, CD123, CD86 and CD83 in the absence of lineage markers (myeloid, B, T or natural killer cells) except for CD33. Culturing leukemic blasts of both cases with IL-3 for 4 days increased the expression of surface molecules associated with antigen presentation, e.g. CD1a and CD40. Leukemic blasts of both cases possessed a considerable level of antigen-presenting ability to allogeneic lymphocytes in mixed leukocyte cultures. Culturing the blasts with IL-3 for 4 days markedly increased allogeneic antigen presenting ability. Combined with data showing evident graft-versus-leukemia effects without graft-versus-host disease in a cord blood stem cell transplanted pDCL case, leukemic cells in pDCL may act as potent antigen presenting cells in vivo, too.
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PMID:Plasmacytoid dendritic cell leukemia with potent antigen-presenting ability. 1894 86


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