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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)

Correlation of thymic changes with the development of CsA-associated syngeneic graft-versus-host disease (sGVHD) suggested that the development of tolerance depends on the prompt regeneration of the thymus after stopping CsA. Accordingly, we have tested recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor I (rhIGF-1) to determine if they accelerate reconstitution of the rat thymus after CsA-induced involution. After 14 days of CsA, the thymus has marked medullary involution but normally recovers fully in 6 weeks. In this study, LEW rats were injected with vehicle, rhGH, or rhIGF-1 for 21 days after stopping CsA and were examined. The vehicle-treated rats showed partial recovery with respect to Hassall's corpuscles, class II antigen expression, medullary size, medullary dendritic cells (DC), and T cell maturation. The mature thymocytes were predominantly CD8+ T cells. Both rhGH and rhIGF-1 induced significant thymic enlargement compared with the vehicle-treated rats. They also both significantly enhanced regeneration with respect to Hassall's corpuscles. The mature thymocyte population had significantly greater CD4+ cells. In addition, rhIGF-1 induced a significant improvement in the medullary size and medullary DC. While the medullae of a normal thymus are in intimate contact with cortical class II antigen, after CsA the cortex adjacent to the medulla is primarily class II antigen negative. RhGH significantly increased the class II antigen in the deep cortex while rhIGF-1 demonstrated a trend toward greater expression in this region (P = 0.06). We conclude that rhGH and rhIGF-1 accelerate thymic regeneration post-CsA. Further studies are now indicated to establish the potential for these factors to enhance the development of antigen-specific tolerance.
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PMID:Enhancement of thymic recovery after cyclosporine by recombinant human growth hormone and insulin-like growth factor I. 194 74

The minor histoincompatible mouse radiation chimera provides a useful model of graft-versus-host disease (GVHD) paralleling conditions in human marrow transplant recipients. While studying the B10.D2/BALB/c model, we noted that a graft-versus-host reaction of particular severity develops in the forestomach near the squamocolumnar junction. Comparison of the dyskeratotic index of this epithelium with that of the skin of the same animal revealed the forestomach to be a more sensitive site for detection of GVHD. In normal mice, both basal forestomach squamous epithelium and cells in the lamina propria expressed class II antigens. During the course of GVHD, class II antigen expression was elevated in the squamous epithelium of the forestomach, the columnar epithelium associated with the stomach, and cells within the associated lamina propria. The demonstration here that the squamocolumnar junction (considered to be a stem cell region for the maintenance of adjacent forestomach squamous epithelium) appears to be a particularly sensitive target tissue in GVHD and earlier identification of other epithelial target tissues of GVHD (hair follicles and rete ridges of epidermis, bile ductules of liver, and crypt cells of the gut) collectively support the hypothesis that GVHD tends to target sites of epithelial proliferation overlying epithelial stem cells.
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PMID:The murine forestomach: a sensitive site for graft-versus-host disease. 207 Jan 31

Previous studies have demonstrated that short-term administration of cyclosporine leads to immunopathologic changes in the thymus, including medullary involution, loss of Hassall's corpuscles, and decreased class II antigen expression. Generally these changes are rapidly reversible. In rats treated with mediastinal irradiation, however, these changes are irreversible and usually associated with autologous or syngeneic graft-vs.-host disease (pseudo-GVHD). This study describes the immunopathology of the thymus after long-term administration of CsA (7 mg/kg/day, up to 140 days) and monitors the recovery post-CsA. The medulla was markedly involuted at the end of CsA, regardless of duration. The relative size of the medulla showed good recovery. Long-term CsA, however, profoundly delayed or prevented the recovery of Hassall's corpuscles and normal expression of class II antigen. The epithelial cells in Hassall's corpuscles totally disappeared at the end of CsA administration. Following 7 or 28 days of CsA, the Hassall's corpuscles recovered within one month. After 70 days CsA, recovery was delayed until the second month, while after 140 days, Hassall's corpuscles were not present even 2 months post-CsA. Class II antigen was decreased in the subcapsular and juxtamedullary regions at 140 days as well as 1 and 2 months post-CsA. Paralleling the thymic immunopathology, acute and chronic pseudo-GVHD were observed in the skin, tongue, liver, intestines, lacrimal glands, bronchi, and intestines following long-term CsA.
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PMID:The thymus and prolonged administration of cyclosporine. Irreversible immunopathologic changes associated with autologous pseudo-graft-versus-host disease. 211 78

The process of graft-versus-host disease (GVHD) elicited by small bowel semi-syngeneic grafts in Lewis rats was studied by an immunohistochemical staining technique for analysis of MHC (major histocompatibility complex) class II antigen expression and of T-cell subpopulations in different organs. Specimens from the graft, native bowel, brain, testis, liver, kidney, and skin were taken on days 5, 10, and 15. All the investigated organs displayed strong class II antigen induction during the course of GVHD. In the native bowel of semi-syngeneically transplanted animals, only discrete morphological changes were noted, whereas the graft displayed a generalized serosal reaction with large infiltrates of rounded and polygonal cells expressing class II antigens. This was not observed in the graft of syngeneically transplanted animals. In the lamina propria of the semisyngeneic graft, 'free' lymphocyte-like cells were depleted and, at the same time, localized aggregates of these cells were observed. Crypt cell class II expression in the native bowel, and to some extent in the graft, was increased during GVHD. However, pronounced intraindividual variations in MHC class II antigen expression were noted, and class II expression was therefore not considered to be a good marker for GVHD.
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PMID:Immunomorphology of graft-versus-host disease after small bowel transplantation in the rat. 220 46

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

To explore the relationship between aberrant MHC antigen expression and tissue injury in acute graft-versus-host disease, we performed a sequential histological and immunohistochemical analysis of multiple tissues in acute GVHD generated across complete MHC and multiple minor H incompatibilities in the rat. Two patterns of MHC antigenic modulation were recognized. Aberrant MHC class I and class II antigen expression occurred simultaneously on the epithelial cells of nonlymphoid target tissues early in acute GVHD. This coincided with a lymphoproliferative phase that preceded nonlymphoid tissue injury. The extent of epithelial class II antigen induction predicted the extent of subsequent histological injury. Changes in MHC class II antigen expression were also seen on nonepithelial cells. Interstitial dendritic cells (IDCs) expressing recipient MHC class II antigens increased in both target and nontarget tissues during early GVHD. Recipient class II antigens were also induced on large numbers of microglialike cells in the brain and Kupffer cells in the liver. However, tissue injury did not follow MHC class II antigen induction on nonepithelial cells. These findings are consistent with a role for aberrant epithelial MHC antigen expression in nonlymphoid tissue injury in acute GVHD.
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PMID:Evidence that nonlymphoid tissue injury in acute graft-versus-host disease is limited to epithelial cells aberrantly expressing MHC antigens. 279 19

Cytokines are proteins produced mainly by lymphocytes in response to an antigenic stimulus. Originally identified and named on the basis of their biological activity, they are now called interleukins; together with the interferons, colony-stimulating factors and tumour necrosis factor/cachectin (TNF) they form a complex and overlapping network of communication between immunocompetent cells. Cytokines play a central role in T cell activation, and interleukin 2 and interferon gamma in particular are involved in the expression of graft-versus-host disease after bone marrow transplantation. Recent studies suggest that TNF is also implicated: the gene encoding TNF is situated close to the MHC gene in both mice and humans, and TNF is able to up-regulate constitutively expressed class II antigen and, with interferon gamma, to induce class II expression in previously normal cells. Bacterial lipopolysaccharide (endotoxin) is a powerful stimulus to TNF, and TNF production may be the mechanism underlying the longstanding observations on the role of the bacterial microflora of the gut in graft-versus-host disease.
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PMID:Cytokines as mediators of graft-versus-host disease. 304 86

In random bred species including dog and man, a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GVHD) in 30% to 50% of the recipients despite the administration of postgrafting immunosuppression. Controlled trials comparing the immunosuppressive drugs methotrexate or cyclosporine have shown no differences in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of combining a brief course of methotrexate with the cyclosporine regimen are now being confirmed in patients with early results indicating a reduction in GVHD and an improved survival. In both species failure to administer immunosuppression after grafting is associated with a high incidence of acute GVHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum reduces the incidence of acute GVHD but at the risk of a higher likelihood of subsequent graft failure and maybe even leukemic recurrence. Results of studies in canine and human chimeras agree with murine data indicating a principal role for T cells in the pathogenic mechanism of GVHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GVHD show proliferative responses to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GVHD. Observations indicate a direct, rather than an indirect, role for T cells in GVHD. "Specific" suppressor cells may be responsible for maintaining stable graft-host tolerance while "nonspecific" suppressor cells may play a role in the impaired immune defenses in patients with chronic GVHD. Chronic GVHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of HLA-identical recipients, particularly following acute GVHD and is more frequent in older patients. Efforts to treat both acute and chronic GVHD with prednisone, antithymocyte globulin, cyclosporine and azathioprine are only unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being pursued in human patients. Marrow grafts from HLA-partially matched family members resulted in a higher incidence of acute GVHD. There was no difference in acute GVHD comparing class I to class II antigen differences and long term survival was influenced by patient age and disease status rather than HLA incompatibility.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-versus-host disease after marrow transplantation. 354 Sep 90

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.
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PMID:Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese. 777 12

In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune response and, thus, provoke the immunopathology of IP.
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PMID:Correlation of interstitial pneumonia with human cytomegalovirus-induced lung infection and graft-versus-host disease after bone marrow transplantation. 857 11


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