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)

One hundred and four patients with acute leukemia treated by allogeneic bone marrow transplantation in Japan were analysed for the incidence of interstitial pneumonitis (IP). Thirty-six (35%) of 104 marrow graft recipients developed IP. Cytomegalovirus (CMV) was the most frequent organism (61%). Using multivariate analysis, remission at transplant (P = 0.0001) and use of cyclosporin A to prevent graft-versus-host disease (P = 0.0363) were found to be significant factors associated with a decreased incidence of IP. For preventing IP, anti-CMV hyperimmune globulin was effective, while interferon and acyclovir were not.
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PMID:Interstitial pneumonitis in allogeneic bone marrow transplantation: a report from the Japanese BMT Study Group. 245 86

Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of restoration of interferon production after bone marrow transplantation in man. 245 87

The epithelium of the biliary tree is involved in the response to numerous liver disease processes including immunologic destruction during liver transplant rejection and liver graft-versus-host disease after bone marrow transplantation. Furthermore, very little is known concerning the function of this previously inaccessible epithelium, because attempts to isolate and culture biliary cells have been unsuccessful until recently. We present a method for the isolation and culture of bile ductular cells from mice with external bile duct obstruction. Over 85% of the isolated cells stain positive for cytokeratin 19, which is characteristic of murine biliary epithelium. Incubation with recombinant murine gamma-interferon resulted in increased class II antigen expression on the isolated cell surface. When these cells were placed, on a basement membrane matrix, they formed duct-like structures composed of cells that had the morphologic characteristics of bile ductular epithelium when examined by transmission electron microscopy. The ability to isolate murine biliary epithelium that forms duct-like structures will be useful for the in vitro study of biliary epithelial characteristics and injury.
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PMID:In vitro duct-like structure formation after isolation of bile ductular cells from a murine model. 247 64

We have been investigating the effects of polyinosinic:polycytidylic acid (pI:C), an interferon inducer, on the graft-versus-host reaction. We have previously shown that pI:C treatment of C57BL/6xAF1 (B6AF1) recipient mice immediately before injection of C57BL/6 (B6) parental lymphocytes inhibited the immuno-suppression and pathological changes normally caused by the GVH reaction, by a mechanism apparently identical to that seen in F1 hybrid resistance (HR) to hematopoietic grafts. We now demonstrate that delaying pI:C treatment by as little as 48 hr produces the opposite effect. Treatment of recipient B6AF1 mice at different days after transfer of parental lymphocytes induced a marked increase in the severity of the GVH reaction, as measured by a decreased plaque-forming cell response to sheep erythrocytes; decreased proliferative response to the T and B cell mitogens PHA, Con A, and LPS; increased pathological changes in both lymphoid and nonlymphoid tissues; and increased GVH-associated mortality. This effect is unrelated to HR, as pI:C was able to augment the severity of the GVH reaction when A strain cells were injected into AxCBAF1 recipients, which do not manifest HR. Early pI:C treatment (1 and 2 days after parental cell transfer) increased the severity of the GVH reaction much more than later pI:C treatment (7 and 8 days after parental cell transfer). This observation, along with the demonstration of altered pathology in GVH mice treated with pI:C, suggests that the effect of pI:C is not mediated through a direct suppressive effect of IF on the cells responding in either the PFC or mitogen assays, but rather by the ability of IF to activate or suppress mechanisms involved in the development of GVH-induced alterations.
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PMID:The effects of polyinosinic:polycytidylic acid on the graft-versus-host reaction. III: Increased severity of the reaction with delayed pI:C treatment. 274 89

T cell phenotypes after bone marrow transplantation (BMT) were investigated using monoclonal antibodies (moAbs) reactive to lymphocyte cell surface antigens. Patients' T cells showed decreased percentages of OKT4, 4A and 9.3-positive T cells, and increased percentages of OKT8, human Ia, and Leu-7-positive T cells. These changes in T cell phenotype persisted for a long period after BMT and had no correlation with the occurrence of graft-versus-host disease (GVHD). No lymphocyte activation antigens such as TIA (Tac) or transferrin receptor (5E9) were detected after BMT. The capacity of the patients' lymphocytes to produce gamma-interferon (IFN-gamma) was measured after incubation of lymphocytes with mitogen. Patients' lymphocytes produced significantly lower levels of IFN-gamma than the normal controls. This failure of IFN-gamma production showed no correlation with stimulation index of mitogen blastogenesis or changes of T cell population. Thus, not only T cell phenotype but also measurement of IFN-gamma production of lymphocyte may be useful in detecting immunological abnormalities in patients who receive BMT.
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PMID:Gamma-interferon production capacity and T lymphocyte subpopulation after allogeneic bone marrow transplantation. 308 47

We have previously reported that mouse bone marrow (BM) cells stimulated with alloantigen produce cytotoxic effector T-cell activity and produce interferon (IFN-)alpha/beta. In this report we show evidence suggesting that interleukin 2 (IL-2) may play a role in this IFN-alpha/beta production by alloantigen-stimulated BM cells. Alloantigen-induced IFN production by bone marrow cells was completely inhibited when cultures were supplemented with antisera to IL-2. Cell-free supernatants obtained at 2 days from cultures containing C57BL/6 BM cells and irradiated DBA/2J spleen cells were also shown to contain low levels of IL-2 activity and induced significant IFN production in fresh BM cells. Different IL-2 preparations were tested for their ability to induce IFN-alpha/beta production in mouse BM cells. Mouse BM cells cultured with recombinant human IL-2 or highly purified mouse IL-2 produced high levels of IFN-alpha/beta activity after 2-3 days of culture with significant IFN activity being detected as early as 24 hr of culture. IL-2-induced IFN-alpha/beta production was partially resistant to irradiation. In contrast, irradiated (2000 rad) bone marrow cells failed to produce any IFN when cultured with alloantigen in the absence of IL-2. T-cell-depleted BM cells or BM cells obtained from C57BL/10 nude mice produced high levels of IFN-alpha/beta following stimulation with IL-2. In addition, bone marrow cells depleted of Ia+, Qa 5+, or Asialo GM+1 cells produced IFN in response to IL-2. Thus, neither T cells nor NK cells are required for IL-2-induced IFN-alpha/beta production by BM cells. The action of IL-2 on bone marrow cells to induce IFN production was mediated by the classical IL-2 receptor, since monoclonal antibodies to the IL-2 receptor present on T cells blocked this response and since bone marrow cells depleted of IL-2 receptor-bearing cells failed to produce IFN when cultured with IL-2. These results suggest that non-T cells resident in the BM have receptors for IL-2 and can produce IFN-alpha/beta upon stimulation by IL-2. Since IFN has been shown to affect different aspects of hematopoiesis, the production of IFN by BM cells stimulated by IL-2 may be important in the control of hematopoiesis. In addition, IL-2-induced IFN production may play a role in graft-versus-host disease.
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PMID:Interleukin 2 induces interferon alpha/beta production in mouse bone marrow cells. 310 59

Immunosuppression is a well-characterized consequence of chronic graft-versus-host disease (GVHD). We have previously shown that interferon (IFN) is produced in high levels during acute GVHD. Our objective in this study was to determine if IFN, as a cytokine with known immunosuppressive qualities, could be detected in mice experiencing chronic GVHD-induced immunosuppression. Two different experimental models were used to induce chronic GVHD. The first model involved the injection of parental strain spleen cells into adult F1 hybrids (AJ----B6AF1), while the second model utilized GVHD induced across minor histocompatibility barriers (B10.D2----BALB/c). Results indicated that significant levels of serum IFN-alpha/beta are present in mice undergoing chronic GVHD. Spleen cells from chronic GVHD mice were also shown to produce significant levels of IFN-alpha/beta upon in vitro culture in medium only. This IFN-alpha/beta production was greatly increased when GVHD spleen cells were cultured with either concanavalin A (Con A) or IL-2. In contrast, IFN-gamma production was undetectable in these Con A- or IL-2-containing cultures. Additionally, these same spleen cells which produced high levels of IFN-alpha/beta were immunosuppressed as measured by mitogen-induced cell proliferation. These results suggest that IFN-gamma production is defective in GVHD spleen cells, and that the presence of high IFN-alpha/beta production by GVHD mice may contribute to the immunosuppression associated with chronic GVHD.
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PMID:Enhanced interferon-alpha/beta (IFN-alpha/beta) and defective IFN-gamma production in chronic graft versus host disease: a potential mechanism for immunosuppression. 311 28

Natural killer lymphocytes can spontaneously kill in vitro a variety of malignant cultured cells. NK cells are present in all normal individuals, and in some species (human, rats) present peculiar morphological features (large granular lymphocytes). They are usually lacking conventional T or B markers, but it appears likely that most NK cells actually are poorly mature cells belonging to the T cell lineage. The physiological control of NK activity is complex. A major role seems to be devoted to the production of interferon. The physiological roles of NK cells are still unknown: they might participate in the control of cell differentiation, in peculiar of hematopoietic precursors and thymocytes; they probably play a role as defense mechanisms during the first days of viral infections; they might be involved in bone-marrow allograft rejection and in acute graft-versus-host disease. However, their actual role in anti-tumor surveillance remains controversial, especially in humans. Nevertheless, NK cells might play some role in the surveillance against leukemias and lymphomas. NK cell defects could participate in the increased occurrence of lymphoproliferative disorders observed in immuno-suppressed patients.
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PMID:[Natural killer lymphocytes. Their role in pathology]. 315 60

Twenty-one patients with acute and chronic leukemia or severe aplastic anemia were studied for NK activity against a thymoma cell line (Thy 121) before and after allogeneic bone marrow transplantation. The means of the pretransplant and post-transplant levels did not differ from the mean of 134 NK determinations in 67 healthy donors. There was no correlation between pretransplant NK levels and the appearance of graft-versus-host disease. Three weeks following bone marrow transplantation, pretransplant NK levels were observed. The sensitivity of NK cells to interferon was the same as in normal donors both before and after bone marrow transplantation. In contrast to methotrexate, cyclosporin A inhibited NK activity in patients and controls in vitro. In vivo cyclosporin A treatment, however, did not decrease NK levels in bone marrow recipients.
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PMID:Natural killer cell activity against a thymoma cell line Thy 121 in bone marrow transplant recipients. 351 2

Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation. The role of interferon (IFN) in GVHD is currently unclear. We have previously shown that interferon (IFN) is produced in vitro by alloantigen-stimulated murine bone marrow cells. This study was initiated to examine whether IFN production occurs in vivo during GVHD. Lethally irradiated mice were given bone marrow (10(7)) and/or spleen cells (2 X 10(7)) from either allogeneic or syngeneic mice. Mice given allogeneic spleen cells or bone marrow and spleen cells showed signs of GVHD within 10 days and usually died within 20 days of transplantation. Mice undergoing GVHD were found to have significant levels of IFN activity in their sera. Serum IFN was detected early (day 3) after transplantation with optimal IFN activity (greater than or equal to 80 units) occurring at 5-6 days. The IFN activity present in the sera obtained from mice with GVHD was identified as IFN alpha/beta by using specific antisera against IFN alpha/beta and IFN gamma. In contrast, irradiated mice given T-cell-depleted allogeneic bone marrow and spleen cells failed to develop GVHD and had no detectable serum IFN activity. Irradiated mice given syngeneic bone marrow and spleen cells or only allogeneic bone marrow cells did not develop GVHD and did not produce detectable IFN activity in their sera. These results show that serum IFN activity correlates well with GVHD and opens for speculation the possibility that IFN may be involved in the pathogenesis associated with GVHD.
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PMID:Interferon alpha/beta synthesis during acute graft-versus-host disease. 354 98


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