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)

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.
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PMID:Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. 759 66

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

Herpes zoster (HZ) has been often observed after bone marrow transplantation (BMT) in childhood. The occurrence of HZ was reviewed in children who received BMT. The clinical features of HZ were reviewed in 44 children who underwent BMT at Kyushu Cancer Center. Among the 35 recipients with a history of varicella before BMT, several factors associated with BMT and the lymphocyte subsets were compared between the patients who developed HZ (HZ+ group) and those who did not (HZ- group). Twenty-two recipients (50%) developed HZ; in two-thirds of these cases (15/22: 68%), HZ occurred between 80 and 120 days after BMT (median 101 days). The recipients treated with busulfan had a higher occurrence of HZ than those treated without it. The patients with Grade II-IV acute graft-versus-host disease (GVHD) developed HZ more frequently. In the HZ+ group, the absolute number of lymphocytes, CD3+, CD4+ or CD8+ cells at 3 months was significantly lower than that observed at 12 months after BMT and the CD4/CD8 ratio was significantly lower at 1 month than after 3 months of BMT. In conclusion, recipients were susceptible to HZ at around 100 days after BMT. The development of HZ may be associated with unbalanced T lymphocytes at that time.
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PMID:Herpes zoster in children with bone marrow transplantation: Report from a single institution. 764 77

The ability of highly purified CD8+ T cells to mediate GVL activity and facilitate engraftment of allogeneic bone marrow cells was studied in the C57BL/Ka-->BALB/c mouse strain combination. Splenic CD8+ T cells were enriched by depletion of CD4+ T cells by "planning" or purified by positive selection by cell sorting. Although C57BL/Ka bone marrow cells reconstitute lethally irradiated BALB/c mice without severe GVHD, the addition of at least 1.0 x 10(6) donor spleen cells induced uniform acute lethal GVHD. Equivalent doses of spleen cells depleted of CD4+ T cells failed to induce lethal GVHD. Allogeneic bone marrow cells alone failed to mediate antitumor activity against the BCL1 B cell leukemia/lymphoma as compared with syngeneic bone marrow and spleen cell injections. Despite the inability to induce severe GVHD, CD4+ T cell-depleted allogeneic spleen cells prevented the progressive growth of the BCL1 tumor, and eliminated BCL1 idiotype-positive tumor cells in the blood. In order to determine whether CD8+ T cells can prevent tumor growth in the absence of other spleen cell subsets, such as NK cells, that are present in the CD4- populations, highly purified CD8+ T cells were obtained by positive selection using flow cytometry. The latter cells prevented the progressive growth of the tumor, and markedly reduced the level of tumor cells in the blood. Sorted CD8+ T cells facilitated the engraftment of allogeneic marrow cells in sublethally irradiated hosts. Thus, addition of highly purified CD8+ T cells to marrow cells provides GVL activity and facilitates engraftment without inducing severe GVHD in most recipients.
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PMID:The role of purified CD8+ T cells in graft-versus-leukemia activity and engraftment after allogeneic bone marrow transplantation. 765 65

In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.
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PMID:Graft-versus-host disease after brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506. 767 53

Acute graft-versus-host disease is a common complication of allogeneic bone marrow transplantation, but the mechanisms resulting in tissue injury are uncertain. In order to probe the effector phase of upper gastrointestinal acute GVHD, we performed immunopathologic studies of duodenal biopsies obtained from patients with or without GVHD. We evaluated the infiltrating mononuclear cells in both epithelium and lamina propria for expression of CD2, CD4, CD8, CD25, T alpha/beta and gamma/delta receptors, CD16, CD56, CD57 and also studied the distribution of cell adhesion molecules (ELAM-1, VCAM-1, ICAM-1, PECAM-1). In the epithelium, only a minimal T cell infiltrate was observed. In the lamina propria, GVHD tissue (vs. control) had an infiltrate of CD2+ (17.7 +/- 2.9% vs. 7.2 +/- 1.8%; P < 0.04), CD8+ (15.5 +/- 4.4% vs. 4.8 +/- 1.9%, P < 0.04) T lymphocytes. GVHD-positive and control tissues contained similar numbers of CD4+ T cells and natural killer cells (CD56+ or CD57+). ICAM-1 staining of endothelial cells was prominent in GVHD tissues (13.5 +/- 1.1 capillaries/field) and was significantly increased over non-GVHD specimens (7.5 +/- 1.8; P < 0.02). ELAM-1, VCAM-1, and PECAM-1 were similarly distributed in both biopsy groups. These data suggest that effectors of upper GI GVHD include CD2+, CD8+, T lymphocytes infiltrating the lamina propria. Inflammatory cell activation and resultant secretion of cytokines might directly damage the mucosa, but may also upregulate ICAM-1 on local endothelium leading to perpetuation of inflammation by recruitment of additional cytotoxic lymphocytes.
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PMID:The immunopathology of upper gastrointestinal acute graft-versus-host disease. Lymphoid cells and endothelial adhesion molecules. 768 Dec 25

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). Because GVHD is frequently refractory to treatment, the early identification of high-risk patients could have significant clinical value. To identify such patients, we examined early immunologic recovery in 136 patients with hematologic malignancies who received anti-T12 (CD6)-purged allogeneic bone marrow over a 9-year period. The majority of patients received marrow from HLA-matched sibling donors after ablation with cyclophosphamide and total body irradiation. No patients received any immune suppressive medications for GVHD prophylaxis. The fraction and absolute numbers of peripheral blood lymphocytes (PBL) expressing the CD3, CD4, CD8, and CD56 surface antigens were determined weekly by immunofluorescence analysis in patients beginning 8 to 14 days (week 2) after marrow infusion. Results in patients who did or did not subsequently develop GVHD post-BMT were compared. Within 2 weeks of marrow infusion, patients who developed grades 2-4 GVHD had significantly higher percentages and absolute numbers of CD8+ T cells and a lower fraction of CD56+ natural killer (NK) cells than individuals who remained free of GVHD. Thirty-five percent of patients whose PBL were greater than 25% CD8+ in the second posttransplant week developed GVHD, compared with only 3% of patients who had < or = 25% CD8+ cells (odds ratio 37.8; 95% confidence interval [CI] 4.1 to 397). A subgroup of patients at very high risk for GVHD could be identified based on the combined frequency of CD8+ T cells and NK cells in blood. Seventy-five percent of patients with greater than 25% CD8+ cells and < or = 45% CD56+ cells during week 2 post-BMT developed GVHD, compared with only 11% of the remaining patients (odds ratio 24.9; 95% CI, 5.3 to 117.0). None of the 23 patients with both less than 25% CD8+ cells and greater than 45% CD56+ cells in the second posttransplant week developed grades 2-4 GVHD. Our findings indicate that CD8+ T cells play an important role in the pathogenesis of GVHD in humans. Analysis of immune reconstitution early after BMT is useful in predicting the onset of GVHD and can help direct the implementation of treatment strategies before the appearance of clinical manifestations. Such interventions may decrease the morbidity and mortality associated with allogeneic BMT and ultimately improve overall survival.
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PMID:Prediction of graft-versus-host disease by phenotypic analysis of early immune reconstitution after CD6-depleted allogeneic bone marrow transplantation. 769 Dec 52

Administration of cyclosporine (CsA) following syngeneic/autologous bone marrow transplantation (BMT) elicits a T lymphocyte-dependent autoimmune disease resembling graft-vs-host disease (syngeneic GVHD). This autoaggression syndrome appears to be due to the autorecognition of self-MHC class II antigens by CD8+ cytolytic T cells and a CD4+ autoreactive T cell subset. The syngeneic GVHD model was used to assess the effectiveness of treatment with monoclonal antibodies to the alpha/beta T cell receptor (TCR) and the CD4 or CD8 determinants on the prevention of autoimmune disease. Nylon wool nonadherent splenic T cells (50 x 10(6)) from Lewis strain rats with active syngeneic GVHD were adoptively transferred into irradiated (1050 rad syngeneic recipients reconstituted with normal marrow (60 x 10(6) cells). Monoclonal antibody (McAb) to the alpha/beta TCR, the CD4 determinant, or the CD8 determinant was administered to secondary recipients on Days 0, 3, 6, 9, and 12 at a dose of 0.1 ml of ascites fluid. Control animals received normal mouse serum on the same schedule. Animals treated with either saline or normal mouse serum developed syngeneic GVHD within 16-20 days. Comparatively, syngeneic GVHD developed much later in the secondary recipients treated with anti-CD4 McAb (onset of syngeneic GVHD, 28-32 days) and was less severe compared to the control group. On the other hand, the recipients treated with McAb's to the alpha/beta TCR or to the CD8 determinant did not develop syngeneic GVHD (monitored over 10 weeks post-therapy). Peripheral blood lymphocytes from these recipients also were analyzed for T cell subsets by phenotypic analysis. There was a pronounced reduction of the total number of cells expressing the alpha/beta TCR and the CD8 determinant after treatment of the recipients with the McAb's to the alpha/beta TCR and to the CD8 determinant, respectively. Recovery to normal levels began to occur 6 weeks after the last dose of McAb. There was a significant reduction of the CD4+ subset after treatment with anti-CD4 McAb, but it was not long lasting with recovery coinciding with the onset of syngeneic GVHD. Studies were also performed to evaluate McAb therapy of established syngeneic GVHD. The McAb's were found to be largely ineffective due in part to pulmonary toxicity. Furthermore, this model was utilized to evaluate the efficacy of treatment with McAb to the target antigen of syngeneic GVHD. Infusion of McAb to a public determinant on class II MHC molecules prevented or significantly delayed the onset of syngeneic GVHD after adoptive transfer of effector cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclosporine-induced syngeneic graft-vs-host disease: prevention of autoaggression by treatment with monoclonal antibodies to T lymphocyte cell surface determinants and to MHC class II antigens. 769 18

Graft-versus-host disease (GVHD) is a life threatening complication that may occur following allogenic bone marrow transplantation (BMT) in the patients with aplastic anemia, leukemia or genetic immunodeficiency. It has been known that GVHD occurs approximately 70% of recipients of BMT in western countries but no definite incidence has been reported in Korea. In our St. Mary's Hospital, GVHD occurs in about 30% of BMT recipients. Histopathologically the acute phase skin shows diffuse lymphocytic infiltrates in the upper dermis with extensive exocytosis. Scattered throughout the epidermis are many degenerated keratinocytes, which are often associated with one or more satellite lymphocytes (satellite cell necrosis). In the chronic phase, acanthosis, eosinophilic keratinocytes resembling colloid bodies and mononuclear cell infiltrates in the upper dermis are noted. We reviewed 5 cases of acute GVHD and 6 cases of chronic GVHD. All patients received allogenic BMT from Jan. 1, 1992 to July 1, 1993. Ten patients were male and one was female. The mean age was 34 (20-70). The pathologic diagnosis was 3 cases of CML, 2 of ALL, 2 of AML (FAB M2), 2 of aplastic anemia, 1 of CLL and 1 of AML (FAB M5). The interval from BMT to GVHD varied from 14 days to 4 years (median 220 days). The skin and GI tract were involved in all eleven cases. Ten cases were histologically proven by skin biopsies, and two cases by salivary gland and colonic biopsies, respectively. The histological findings of the skin, salivary gland and colonic biopsieds were described. Immunohistochemical stain of the skin was done using CD4, CD8, HLA DR and Leu 7 antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Graft-versus-host disease--clinical and pathological analysis of 11 biopsy proven cases. 770 86

Polyclonal antithymocyte globulin (ATG)/antilymphocyte and antilymphoblast globulins (ALG) antibodies have been used successfully in transplantation, aplastic anemia and graft-versus-host disease. Flow cytometry has been used to analyze peripheral blood lymphocyte populations in transplant patients receiving polyclonal ATG/ALG preparations for immunosuppression. Recent reports have indicated clinical dose adjustment based on levels of patient's cells expressing various CD antigens. In vitro analysis of individual polyclonal ATG/ALG CD antigen specificity could identify appropriate antigens for clinical monitoring as well as provide useful in vitro activity data. Therefore, a flow cytometry based assay to characterize and compare activities to specific CD antigens found on the surface of peripheral blood lymphocytes has been developed. Activities found in four lots each of horse ATG (ATGAM, Upjohn), rabbit and horse ATG (thymoglobulin and lymphoglobulin, Merieux), horse ALG (Minnesota), and rabbit ATG (Fresenius) have been compared for CD2, CD3, CD4, CD5, CD7, CD8, CD11a, CD18, CD28, CD44, CD45, and TCR-alpha/beta antigens. Quantitation is achieved by measuring the concentration of ATG/ALG required to give 50% inhibition of antigen specific fluorescent-labeled monoclonal antibody relative to buffer controls. The three horse products tested have similar activity to most antigens tested. However, Fresenius rabbit ATG has the lowest activity for almost all antigens tested whereas the Merieux rabbit ATG has activities closer to the horse products. This technique allows for rapid in vitro comparison of reactivities to individual lymphocyte antigens as well as in vitro analysis of consistency.
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PMID:Comparative polyclonal antithymocyte globulin and antilymphocyte/antilymphoblast globulin anti-CD antigen analysis by flow cytometry. 773 66


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