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)

Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease (GVHD). However, optimal dosage is still under debate. Thirty-one consecutive children, mainly with haematological malignancies, were transplanted in a single institution with such donors, selected by HLA-A -B compatibility by serology and DRB1* by DNA typing. Antithymocyte globulin (Thymoglobuline; Sangstat) was infused at days -3, -2, -1. Total dosage varied: 16 patients received a median of 7.5 mg/kg (2.5 to 10.5: low-dose group), and 15 a median of 15.5 mg/kg (14.4 to 19.4: high-dose group). Post-transplant GVHD prophylaxis consisted of cyclosporine, short-course methotrexate and steroids. CD3(+), CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group. Median time to reach 100 CD4(+) cells was 8 months vs 4 months (P = 0.03). Median time to normal CD19(+) cells was 16 months vs 8 months (P = 0.01). CD16(+)CD56(+) and CD8(+) cell reconstitution was similar. Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections (P = 0.009). Although obtained from a limited number of patients, our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution.
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PMID:Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin. 1236 53

To compare the expression of CD antigens on immune cells from umbilical cord blood (UCB) and bone marrow (BM) and analyze its clinical significance, the phenotypes of lymphoid cells and nucleated cells from 38 UCB and 10 BM samples were investigated by flow cytometry with double labeling monoclonal antibodies. The results showed that the immature lymphocytes (CD3(-) CD4(+)) were detected in UCB and higher than those in BM; cytotoxic T lymphocytes (CD3(+) CD16(+) CD56(+)) in UCB were significantly lower than those in BM. NK cells (CD3(-) CD16(+) CD56(+)) in UCB were higher than those in BM. The ratio of CD34(+) cells in nucleated cells of UCB was similar to that of BM, however, both the contents of myeloid (CD34(+) CD13(+) and CD34(+) HLA-DR(+)) and lymphoid (CD34(+) CD19(+)) progenitor cells in UCB were lower than those in BM. It is concluded that the immune cells in UCB possess immaturity, which might lead to mild GVHD after UCB transplantation. It is inferred from the higher ratio of NK cells in UCB, GVL will not decrease after UCB transplantation. The lower contents of myeloid and lymphoid progenitor cells in UCB probably accounted for the slow hematopoiesis and immune reconstitution following UCB transplantation.
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PMID:[A comparison between immunophenotypes of lymphoid cells from human umbilical cord blood and bone marrow and its significance]. 1251 12

In recent years, umbilical cord blood has emerged as an alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack an human leukocyte antigen-matched marrow donor. Since 1998, about 2,500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg, however more than 500 UCB transplantations have already been performed in adults. The "naive" nature of UCB lymphocytes may explain the lower incidence and severity of graft versus host disease encountered in UCBT compared to the allogeneic transplant setting. Furthermore, UCB is rich in primitive CD16-CD56++ natural killer cells, which possess significant proliferative and cytotoxic capacities and can be expanded using interleukin-12 or 15, so as to mount a substantial graft versus leukemia effect. The major disadvantage of UCB is the low yield of stem cells, resulting in higher graft failure rates and slower time to engraftment compared to bone marrow transplantation. A rational approach thus involves ex vivo expansion of UCB-derived hematopoietic precursors.
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PMID:Cord blood biology and transplantation. 1474 May 9

Umbilical cord blood transplants are associated with a lower incidence of graft-versus-host disease (GVHD) than adult marrow or peripheral blood stem cell transplants, and this could be related to a difference in cytokine production between fetal and adult mononuclear cells after allogeneic stimulation. Mixed lymphocyte reactions (MLRs) involving adult cells were associated with greater interferon-gamma (IFNgamma) secretion than MLRs between cord blood cells, although IL-2 secretion was similar. Experiments in which T cells were separated from accessory cells then recombined in artificial combinations indicated that differences in T cells were primarily responsible for the greater [IFNgamma]:[IL-2] ratios generally found after MLRs involving adult cells compared to fetal cells, but accessory cells also influenced this ratio. The cellular basis for the observed difference was not established, but mononuclear cell preparations from cord blood contained significantly higher proportions of CD16(+)56(-) NK-type cells and a CD19(+)1c(+) B cell subset, as well as more CD45 RA-expressing nai;ve T cells.
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PMID:Comparison of adult and fetal cytokine secretion during mixed lymphocyte reactions. 1475 70

Dendritic cells (DCs) play a pivotal role in the activation of T cells, which are effector cells in graft-versus-host disease (GVHD). A low incidence of GVHD following cord blood (CB) transplantation has long been reported; despite this, little information is currently available on the characteristics of CB DCs. The goal of the present study was to investigate the immunophenotypic characteristics and distribution of CB DCs and their subsets. For that purpose we have analyzed 15 CB samples as compared to normal peripheral blood (PB) (n = 7) and blood from patients submitted to an allogeneic PB stem cell transplantation (allo-PBSCT) (n = 6). Our results show an overall decreased frequency of DCs in CB due to the presence of significantly lower numbers of CD123inter./CD33inter./CD16+ DCs. Phenotypically, CB DCs displayed a tendency to express lower levels of the gamma-chain interleukin-2 (IL-2) receptor (CD132) and of the CD86 co-stimulatory molecule, supporting a higher degree of immaturity for CB as compared to PB DCs. After activation of CB DCs with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) higher frequencies of cytokine-producing cells were found among CD123inter./CD33inter./CD16+ and CD123dim/CD33bright/CD16- DCs; however, when only the cytokine-producing DCs were considered, a significant decrease in the amount of different cytokine (e.g., IL-1beta and IL-6) produced per cell was observed especially for CD16+ CB DCs. These findings support a higher degree of immaturity for CB as compared to PB DCs that might contribute to explain, at least in part, the low incidence and severity of GVHD observed after CB transplantation.
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PMID:Immunophenotypic and functional characterization of cord blood dendritic cells. 1506 94

In recent years, umbilical cord blood (UCB) has emerged as a feasible alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack HLA-matched marrow donors. Since the first case reported in 1998, more than 3500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg; however, more than 500 UCB transplantations (UCBTs) have already been performed in adults. The "naive" nature of UCB lymphocytes also permits the use of HLA-mismatched grafts at 1-2 loci without higher risk for severe graft versus host disease (GvHD) relative to bone marrow transplantation (BMT) from a full matched unrelated donor. Furthermore, UCB is rich in primitive CD16(-)CD56++ NK cells, which possess impressive proliferative and cytotoxic capacities and can be induced to expand using IL-12 or IL-15, so as to mount a substantial graft versus leukemia (GvL) effect. The main disadvantage of UCB is the low stem cell yields, resulting in higher rates of graft failure as well as delayed time to engraftment compared to BMT. One rational approach to overcome this limitation involves ex vivo expansion of UCB derived hematopoietic precursors. In this review we tried to answer the question: UCBT how, when and for whom. This procedure is mostly applicable for children and especially those with indication for full allogeneic transplantation but who lack a matched sibling donor. Experimental approaches including ex vivo expansion of CB with cocktail of hematopoietic growth factors, with or without differentiation blocking agents, co-transplantation of haploidentical and CB cells or co-transfusion of CB and mesenchymal cells may enable successful UCBT in adults and probably will result in expanding the indication to solid tumors or autoimmune disorders.
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PMID:Umbilical cord blood transplantation--how, when and for whom? 1518 1

To investigate the changes of donor's peripheral blood immunocytes after mobilization with medium-dose recombinant human granulocyte-colony stimulating factor (rhG-CSF), the amounts of immunocytes in peripheral blood cells and the immunocyte components of donor peripheral blood mononuclear cells (PBMNC) in 12 healthy donors were detected by flow cytometry before and after mobilization with rhG-CSF 10 microg/(kg.day). The results showed that the median amounts of peripheral blood leukocytes before mobilization was 6.25 (4.7-7.8) x 10(9)/L, for lymphocytes it was 2.07 (1.63-3.10) x 10(9)/L, and for monocytes it was 0.163 (0.078-0.414) x 10(9)/L. In the fifth day after mobilization, the median amounts of peripheral blood leukocytes was 37.47 (24-72.57) x 10(9)/L, and for lymphocytes it was 3.22 (1.46-5.31) x 10(9)/L, and for monocytes, it was 1.2 (0.706-3.627) x 10(9)/L. The average amount of leukocytes after mobilization was 6.26 +/- 2.14 multiple of that before mobilization (P < 0.01), and the median amounts of lymphocytes after mobilization was 1.45 +/- 0.76 multiple of that before mobilization (P < 0.05), and the amount of monocytes after mobilization was 7.48 +/- 4.41 multiple of that before mobilization (P < 0.01). The median percentage of CD3(+) T lymphocytes before mobilization was 46.96% [(32.36-57.45)%], but 40.94% [(25.31-48.9)%] after mobilization. The ratio of CD4(+)/CD8(+) before mobilization was 1.27 +/- 0.46, while 1.36 +/- 0.51 after mobilization. The median percentage of CD4(+)CD8(+) T lymphocytes was 0.41% [(0.16-1.51)%], and 0.49% [(0.09-2.0)%] after mobilization. The median percentage of CD16(+)CD56(+) NK cells was 13.98% [(4.08-25.08)%] versus 16.65% [(12.06-33.05)%] after mobilization. The median percentage of CD3(+)CD16(+)CD56(+) NK-T cells was 2.75% [(0.37-6.38)%], but 3.13% [(0.46-5.95)%] after mobilization. The median percentage of CD20(+) B cells was 9.28% [(5.97-16.33)%], while 9.94% [(7.36-20.41)%] after mobilization. The median percentage of CD14(+) monocytes was 12.48% [(3.54-19.35)%] versus 29.52% [(16.51-36.76)%] after mobilization. The percentage of CD3(+) T lymphocytes, CD4(+)CD8(+) T lymphocytes, NK cells, NK-T cells and B lymphocytes in PBMNC did not change markedly before and after mobilization with middle-dose rhG-CSF. The ratio of CD4(+)/CD8(+) did not change significantly (P > 0.10). The percentages of CD14(+) monocytes in PBMNC after mobilization increased up to 2.87 +/- 1.51 higher than that before mobilization (P < 0.05). It is concluded that the changes of the CD14(+) monocytes after mobilization with rhG-CSF may be involved in graft rejection and graft versus host disease after allo-PBSCT.
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PMID:[Effects of mobilization with medium dose of rhG-CSF on the immunocyte component of peripheral blood in donors]. 1627 57

Cyclosporin A (CSA) is commonly used to prevent graft-versus-host disease. The influence of CSA on T-cell function has been extensively investigated; however, the effect of CSA on natural killer (NK) cells is less understood. NK cells were cultured with IL-2 and IL-15 with and without CSA for 1 week. Compared with controls, CSA-treated cultures showed fewer CD56(+)CD16(+)KIR(+) NK cells and a reciprocal increase in CD56(+)CD16(-)KIR(-) cells. These changes were due mainly to a reduced proliferation of the CD56(dim) NK-cell subpopulation and a relative resistance of CD56(bright) NK cells to CSA. Following coculture with K562 targets, CSA-exposed NK cells differed from controls and lacked Ca(2+) oscillations, nuclear factor of activated T cells (NFAT) dephosphorylation, and NFAT nuclear translocation. NK cells cultured in CSA retained cytotoxicity against K562, Raji, and KIR ligand-expressing lymphoblastoid cells. NK cells cultured in CSA showed increases in NKp30 and reductions in NKp44 and NKG2D. Following IL-12 and IL-18 stimulation, CSA-treated NK cells showed more IFN-gamma-producing cells. Using in vitro NK-cell differentiation, progenitor cells gave rise to more CD56(+)KIR(-) NK cells in the presence of CSA than controls. Collectively, these studies show that CSA influences NK-cell function and phenotype, which may have important implications for graft-versus-leukemia effects.
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PMID:The unexpected effect of cyclosporin A on CD56+CD16- and CD56+CD16+ natural killer cell subpopulations. 1749 33

Human umbilical cord blood (CB) has recently been used as a source of stem cells in transplantation. NK cells derived from CB are the key effector cells involved in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). It was reported that the activity of CB NK cells was lower than that of adult peripheral blood (PB) NK cells. In this study, we analyzed the expression of some NK cell receptors and cytotoxicity-related molecules in CB and PB NK cells. The expressions of activating NK receptors, CD16, NKG2D and NKp46, did not show significant difference between CB and PB NK cells. But the expression of inhibitory receptor NKG2A/CD94 was significantly higher on CB NK cells. As to the effector function molecules, granzyme B was expressed significantly lower in CB NK cells, but the expressions of intracellular perforin, IFN-gamma, TNF-alpha and cell surface FasL and TRAIL did not show difference between CB and PB NK cells. The results indicated that the high expression of NKG2A/CD94 and low expression of granzyme B may be related with the reduced activity of CB NK cells.
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PMID:High expression of NKG2A/CD94 and low expression of granzyme B are associated with reduced cord blood NK cell activity. 1797 18

Umbilical cord blood (UCB) has been used as an alternative source of haematopoietic progenitors for transplantation presenting advantages over bone marrow (BM) that are related with known shortages of newborns' immune system at adaptive and innate levels. Using flow cytometry, we studied the expression of Toll-like receptors (TLRs) and chemokine receptors (CKRs) and the production of pro-inflammatory cytokines by monocytes and CD14(-/low)/CD16(+)DCs from peripheral blood (PB; n=10), and umbilical cord blood (UCB; n=10). CKRs and cytokines were studied before and after stimulation of cells with LPS plus IFN-gamma. We also identified the two populations in normal bone marrow samples (BM; n=5). BM presented lower frequencies of both studied populations when compared to UCB and PB. CD14(-/low)/CD16(+)DCs presented a pattern of TLR expression different from mature monocytes reflecting distinct functions for these two populations. UCB cells presented reduced expression of TLR-4 and lower capability to produce cytokines prior stimulation. The populations studied presented different patterns of CKR expression reflecting distinct migratory pathways. Moreover, UCB cells presented higher expressions of CXCR4 and CCR7 that may be involved in immune system maturation and stem cell homing. Monocytes and CD14(-/low)/CD16(+)DCs present functional and phenotypical characteristics that may contribute to the lower incidence and severity of GVHD.
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PMID:The phenotypical and functional characteristics of cord blood monocytes and CD14(-/low)/CD16(+) dendritic cells can be relevant to the development of cellular immune responses after transplantation. 1834 38


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