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)

Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD.
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PMID:Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy. 259 86

T cell clones (n = 456) were derived from 9 patients following allogeneic bone marrow transplantation (BMT) with or without acute graft versus host disease (aGVHD) and from 4 healthy donors. The cloning efficiency was 63.2% in controls, 13.2% and 12.1% in patients with or without aGVHD. Once established, T cell clones were typed for surface markers (CD3, CD4, CD8) and tested for production of IL-2 and expression of cytolytic activities in a lectin-dependent cellular cytotoxicity assay (LDCC) and against the K562 target cell line to detect natural killer activity. We found the expected imbalance of CD4/CD8 clones in BMT patients, as compared to controls. A higher proportion of IL-2-producing clones was observed in patients with aGVHD (83.5%; P less than 0.02) as compared to patients without aGVHD (64.8%) and controls (68.5%). No major differences were found in terms of LDCC, whereas an increased percentage of clones with NK-like activity was found in patients with aGVHD (34.7%, P less than 0.05) as compared to patients without aGVHD (29.5%) and controls (21.3%). The clones were also tested for inhibition of IL-2 production mediated by cyclosporine. Such inhibition could be obtained in virtually all clones both in patients with or without aGVHD, suggesting that the latter is probably not due to the emergence of CsA-resistant clones. In conclusion, this study demonstrates a low cloning efficiency in BMT patients associated with the well-known CD4/CD8 imbalance. A higher production of IL-2, an increased NK activity, but not the presence of CsA-resistant clones appear to differentiate patients with from patients without aGVHD.
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PMID:Phenotypic and functional characterization of T cell clones following allogeneic bone marrow transplantation. 265 22

The survey of the characteristics of HIV infection implicates the binding of HIV env to the CD4 receptor as the principal cause of the resulting immunodeficiency. There is evidence that such binding selectively impairs self-recognition. The resulting immunodeficiency syndrome has the characteristics of graft vs. host disease, consistent with chronic allogeneic and semiallogeneic GVHD in mouse-models. since these syndromes are believed to result from triggering the established immunoregulatory mechanisms necessary to maintain self-tolerance, vaccination to prevent AIDS should aim to correct the inability of the HIV host mount an immune response against CD4 binding epitopes on HIV gp120, preferably without exposing the vaccine to intact envelope glycoprotein. Since the AIDS syndrome is probably a defect in net-work immunoregulation, the most appropriate target for therapy and for vaccination is the idiotype of anti-CD4 antibodies that block CD4/env interaction.
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PMID:The relevance of HIV env/CD4 interactions to the pathogenesis of acquired immune deficiency syndrome. 267 11

71 leukaemic patients having HLA-matched bone-marrow transplants (BMT) were randomised to receive whole marrow (group A) or marrow depleted of T cells by treatment with monoclonal antibodies (anti CD4-CD5-CD8, group B; anti CD2-CD5-CD7, group C) plus complement. All patients received cyclophosphamide and total body irradiation before transplantation and cyclosporin after BMT. Marrow treatment removed 97% of T cells (median) in group B and 99% in group C. Although both serious and mild graft-versus-host disease (GVHD) were reduced in T-cell depleted patients, graft failure and relapse were increased. Graft failure was caused by GVHD and transplant complications in the controls and by rejection and relapse in the T-cell depleted groups; relapse-free survival did not differ between the groups. Without better control of host immunity and of the residual leukaemia T-cell depletion of the marrow, BMT should not be pursued in standard-risk patients.
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PMID:Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. 288 38

It has previously been demonstrated that graft-versus-host disease can be overcome in patients receiving HLA-mismatched bone marrow transplants by prior in vitro depletion of T lymphocytes from the marrow. In this report we describe the use of monoclonal antibodies and magnetic microspheres for the depletion of T cells from peripheral blood and bone marrow. The target cells are sensitized with antibodies directed against the CD2, CD3, CD4 and/or CD8 cell surface antigens, captured by magnetic beads coated with sheep anti-mouse IgG antibody and collected by placing the cell suspension in a magnetic field. This simple, rapid procedure results in the efficient removal of T cells from peripheral blood and from bone marrow without affecting the colony-forming potential of normal hematopoietic stem cells. The procedure is capable of being scaled up for the treatment of larger volumes of marrow that are required for clinical transplantation.
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PMID:T lymphocyte depletion of human peripheral blood and bone marrow using monoclonal antibodies and magnetic microspheres. 290 78

An in vitro skin explant model for graft-versus-host disease (GVHD) in humans has been used to study the role of effector T cells in the histological pathogenesis of GVHD. In 11 of 12 experiments clear GVHD changes of grades II-IV were induced in HLA-mismatched skin explants cultured with allogeneic T cells sensitized by in vitro mixed lymphocyte culture. The role of effector T cells was investigated by comparing results before and after removal of CD3 positive cells, and CD4 positive and CD8 positive T cell-subsets by antibody and complement cytolysis from responder populations. Only total removal of CD3 positive T cells prevented histopathological lesions of GVHD in the skin biopsy specimens. The results also demonstrated that the CD4 positive population caused the greatest degree of GVHD in vitro in skin biopsy specimens and direct infiltration into skin by cells is not required for changes to become evident. These results confirm the early results on animal models and demonstrate the use of the skin explant model as a tool for studying the biology of GVHD in humans.
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PMID:Skin explant culture as a model for cutaneous graft-versus-host disease in humans. 297 10

Cyclosporin A (CsA) acts as a powerful immunosuppressive agent, and also, when given in repeated doses, can cause T-cell-dependent graft-versus-host disease and organ-specific autoimmune disease in rodents. This suggests that CsA interferes with the processes governing self-tolerance, either by nullifying the activity of T suppressor cells or by preventing the deletion of autoreactive T cells during ontogeny in the thymus. We report here that irradiated mice given repeated injections of CsA show striking dysfunction of the thymus. There are two different effects, the first of which is that CsA seems to block the differentiation of immature CD4+CD8+ thymocytes into mature CD4+CD8- and CD4-CD8+ cells expressing a high density of T-cell receptors and CD3 molecules. Second, CsA-treated mice show incomplete deletion of T cells expressing T-cell receptor molecules reactive to self H-2 I-E molecules.
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PMID:Abnormal differentiation of thymocytes in mice treated with cyclosporin A. 297 33

Cyclosporine-induced pseudo-graft-versus-host disease (CIPGVHD) in syngeneic or autologous rat marrow chimeras has clinical and histologic features closely resembling classic graft-versus-host disease in the allogeneic chimera. We describe here the pathology and immunopathology of the usual target tissues in CIPGVHD developing in the first week following CsA (early group). The findings are constrasted to the CIPGVHD developing during the second week post-CsA (later group). Six of 9 rats in the early group had acute-type CIPGVHD in the tongue, skin, liver, intestines, and mainstem bronchi. In general, the lymphocytic infiltrates in these tissues were in intimate contact with injured epithelial cells. The intestines had multiple apoptotic lesions. Class II antigen was prominent in the tongue mucosa, but only patchy expression was evident in 2 skin biopsies. All of the lymphocytes infiltrating the mucosa were CD8+(OX-8)/CD4-(W3/25) T cells (OX-19+). Most of the lymphocytes in the lamina propria expressed CD4 as well as CD8 markers, suggesting coexpression. In the later group, 6 of 7 rats had chronic-type CIPGVHD (1 with acute and chronic) while 1 rat had no GVHD (P = .02, Fisher's exact test compared with the early group). These animals had features characteristic of established chronic GVHD in the skin, tongue, liver, intestines, and salivary glands. Fibrosis of the dermis and lamina propria was prominent in the skin and tongue. Submucosal fibrosis was increased in the small intestine. The salivary glands had an interstitial infiltrate and fibrosis with loss of ducts and glands. Class II antigen was prominent in the epidermis of the tongue and skin of all rats. The number of lymphocytes infiltrating the mucosa of the tongue was considerably smaller than seen in the early group. More than 90% of these cells were T cells, as detected by OX-19, and expressed both CD4 and CD8 markers. While most lamina propria lymphocytes expressed the CD4 antigen, there were significantly fewer CD8+ cells, consistent with increased numbers of CD8-/CD4+ helper-phenotype cells. The observations indicate that immediately post-CsA, the CIPGVHD is primarily acute, with epithelial infiltrates of CD8+/CD4- T cells and lamina propria infiltrates that include double-labeled cells consistent with immature thymocytes. There is a rapid transition to established chronic-type CIPGVHD by the second week. The residual mucosal infiltrate is now dominated by double-labeled T cells or thymocytes while the lamina propria infiltrate has more mature helper-phenotype T cells. Induced RT1.B/D antigen could be important in the pathogenesis of the peripheral tissue manifestations.
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PMID:Cyclosporine-induced pseudo-graft-versus-host disease in the early post-cyclosporine period. 304 92

The effect of cyclosporine on a systemic graft-versus-host reaction, cardiac allograft rejection, and a local host-versus-graft reaction in the rat were examined in detail. Therapeutic levels of CsA did not inhibit the early stages of lymphocyte activation but did prevent maturation of the immune response to full effector function--viz., graft rejection or clinical GVH disease. In all three models the phenotype changes in T cells associated with the early stages of activation--i.e., induction of receptors for interleukin 2 (IL-R), induction of MHC class II expression, and coexpression of CD4 and CD8 glycoproteins--were not inhibited by CsA. In the GVH and HVG reactions lymphocyte activation proceeded as far as DNA synthesis. In the systemic GVH model animals showed no sign of GVHD for as long as CsA was administered, but withdrawal of the drug resulted in accelerated lethal GVHD.
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PMID:T cell activation in the presence of cyclosporine in three in vivo allograft models. 304 98

Graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) is initiated by immunocompetent T cells present in the graft. Selective elimination of distinct T-cell subsets or a sufficient, but not complete T-cell depletion, might abolish severe GVHD without graft rejection and loss of the anti-tumour potential. In this study we analysed the efficacy of different monoclonal antibodies (MoAb) WT32 (CD3), OKT4 (CD4), T101 (CD5), WT1 (CD7), and WT82 (CD8) with respect to their cytotoxicity to T cells either as immunotoxin (IT) or in combination with complement. The cytotoxic potential was assessed by protein synthesis inhibition and clonogenic assays. The ricin A conjugated MoAb exerted only a minor effect on blood or bone marrow T cells, although they were highly inhibitory to T-cell lines. However, in the presence of 20 mM ammonium chloride, IT directed against CD3, CD5, and CD7 were highly cytotoxic. IT directed against CD4 and CD8 were less effective, due to a low internalization. The complement-mediated cytotoxicity was efficient for all antigens used. The natural killer (NK) activity, as measured by cytotoxicity to K562, was hardly depressed by anti-CD3, anti-CD4, anti-CD5, and anti-CD8, but was eliminated by anti-CD7. All procedures used had only a minimal effect on haematopoietic progenitors as measured by CFU-GM and BFU-E assays. We concluded that, although the T-cell population can be eliminated with the combination of anti-CD3, anti-CD5, and anti-CD7 antibodies plus complement, IT with 20 mM NH4Cl appear to kill higher amounts of T cells. Selective elimination of CD4- and CD8-positive cells is effectively obtained by MoAb with complement.
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PMID:Human T lymphocyte differentiation antigens as target for immunotoxins or complement-mediated cytotoxicity. 326 84


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