UMLS:C0018133 - FACTA Search

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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)

This study was performed to characterize the intestinal lesions in chronic graft-versus-host disease (GVHD) in mice and to determine a possible role of intestinal intraepithelial lymphocytes (ilEL) in the development of these lesions. Chronic GVHD was induced by transfer of DBA/2 lymphocytes into non-irradiated (C57BL/10 x DBA/2)F1 (BDF1) recipients. There was mild to moderate mucosal oedema with multifocal mixed inflammatory cell infiltrations in the small intestine. The caecum was more severely affected with severe oedema, progressive loss of crypts and severe distortion of the mucosal architecture. The total number of ilEL did not change during the development of chronic GVHD, but there were alterations in the composition of the ilEL population. An increase of CD3+, Thy-1+ cells was accompanied by an increase of TCR alpha beta + cells and a decrease of TCR gamma delta + cells. There was no evidence of infiltration of donor lymphocytes into the intestinal epithelium as determined by the H2K haplotype of the ilEL. These lesions differ from previously described models of chronic GVHD, induced by DBA/2 donor lymphocytes in BDF1 recipients. We suggest that the haemopoietic organs that are used as the source of donor lymphocytes determine the outcome of the GVHD. Modulation of the composition of the donor lymphocyte population may be useful in the establishment of relevant animal models of human enteropathy.
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PMID:Effect of chronic graft-versus-host disease on the intestine in adult BDF1 mice. 839 10

Murine graft versus host (GVH) disease takes two forms depending on the parental/F1 strain combination employed. In an accompanying paper (Singh et al., Clin. Immunol. 151, 1993) many of the clinical features of these two forms of GVH disease are described. In addition to these clinical characteristics, acute lethal GVH (ALGVH) disease is characterized by diminished natural killer cell activity, whereas chronic GVH disease is characterized by normal or increased natural killer cell activity. Previously we have reported that this marked disparity in disease expression can be attributed to radiosensitive host cells which protect the F1 mouse from parental anti-F1 cytotoxicity (CTX) in mice undergoing chronic GVH (CGVH) disease. These cells fail to functionally emerge in mice undergoing ALGVH disease. We now report that the background genome, presumably the minor lymphocyte stimulatory loci, of the donor cells determines whether these host cells emerge and thereby dictates the form of GVH disease which is induced. C57BL/6 (B6) cells (H-2b, minor lymphocyte stimulatory locus (Mls)b) and B10.D2 cells (H-2d, Mlsb) were found to induce ALGVH disease when adoptively transferred to [C57BL/6xDBA/2]F1 (B6D2) (H-2b/d, Mls-1a/b, Mls-2a/b) recipient mice. DBA/2 cells (H-2d, Mls-1a, Mls-2a) and Balb/c cells (H-2d, Mls-1a, Mls-2b) induced CGVH disease in B6D2 mice. Using Mls congenic strains we have demonstrated that donor cell reactivity against Mls-2a was necessary and sufficient to induce ALGVH disease as determined by anemia, lymphopenia, anti-F1 cytotoxicity, and loss of cytotoxicity against allogeneic targets. Such Mls-2a reactivity correlated with the impaired induction of a host protective cell capable of vetoing self-directed CTX. Failure of this host protective cell to emerge in turn correlated with donor anti-host CTX and the emergence of ALGVH disease.
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PMID:The host response in graft versus host disease. II. The emergence of host protective cells is in part determined by background genomic compatibility. 840 30

The injection of DBA/2 parental lymphocytes into adult, immunologically intact (C57BL/6 x DBA/2) F1 hybrid mice results in a chronic graft-vs-host reaction (GVHR) characterized by a deficiency in CD4+ T cell functions and a B cell activation leading to autoantibody production. The discovery that distinct subpopulations of Th cells may regulate the effector immune functions led us to investigate whether the chronic GVHR differentially affects Th subsets. Data are presented indicating that mice undergoing a GVHR spontaneously produced lymphokines of Th2 origin. IL-4 and IL-10 mRNA were detected in the spleens of GVH mice, and IL-4 was shown to be responsible for the increased expression of class II Ag on B cells. Moreover, upon polyclonal activation in vitro, GVH T cells exhibited defective IL-2 and IFN-gamma production but elevated IL-4 production. We conclude that the chronic GVHR is characterized by a selective deficiency in cells secreting IL-2 and IFN-gamma and a hyperactivation of Th2 cells. The simultaneous production of IL-4 and IL-10 might explain the association between B cell hyperactivity and impairment of Th1-like activities in various models that associate autoimmunity and immunosuppression, such as GVHR and HIV infection.
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PMID:Preferential activation of Th2 cells in chronic graft-versus-host reaction. 841 69

The relationship between acute and chronic graft-versus-host disease (GVHD) is not well understood. While both syndromes appear to result from recognition of host antigens by donor T cells, their pathological changes differ markedly. In light of the recent concept that helper T cells (Th) may be divided into two types based on their cytokine secretion profile and their ability to mediate cellular (Th1) or humoral (Th2) immunity, and considering the inflammatory nature of acute GVHD and the occurrence of significant B cell activation in chronic GVHD, we hypothesized that acute and chronic GVHD may be associated with differential cytokine production by activated T cells. To evaluate this hypothesis, we assessed expression of a range of cytokines in (C57BL/6 x DBA/2)F1 (B6D2F1) recipients of C57BL/6 (acute GVHD), DBA/2 (chronic GVHD) or B6D2F1 (control) spleen cells. The results reported here indicate that a wide range of cytokines, including interleukin (IL)-4, IL-10, interferon-gamma, tumor necrosis factor beta and macrophage inflammatory protein-1 alpha, are indeed differentially expressed in acute and chronic GVHD and support the concept that the pathology peculiar to acute or chronic GVHD may arise due to differential cytokine expression by activated T cells.
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PMID:Differential cytokine expression in acute and chronic murine graft-versus-host-disease. 843 68

Autoimmune diseases are far more common in women than in men. In the incidence of systemic lupus erythematosus (SLE), the female-to-male ratio is as high as 10:1. This suggests that sex hormones may play a fundamental role in determining the susceptibility to these diseases. In order to investigate the sex-related differences in the inducibility of chronic graft-versus-host disease-related experimental lupus nephritis, lymphocytes from female DBA/2 donor mice were administered to either male or female (C57BL10 x DBA/2)F1 recipients. An additional group of male recipients received lymphocytes from male DBA/2 donors. After four cell transfers, female recipients developed a significantly higher albuminuria than both male groups. Serum concentrations of autoantibodies against glomerular basement membrane (GBM), collagen IV, and laminin were significantly higher in females 2-4 weeks after induction. Levels of circulating autoantibodies against renal tubular epithelial antigens (RTE) and nuclear antigens were not different between the sexes. In transfer studies, the necessity of the presence of anti-GBM and anti-RTE autoantibodies for the development of glomerulonephritis was confirmed. These findings indicate that: (i) in this model of lupus nephritis, susceptibility to glomerulonephritis is strongly influenced by sex-related genes; and (ii) among the variety of autoantibodies occurring in this model of SLE, both anti-GBM and anti-RTE autoantibodies play a key role in the pathogenesis of glomerulonephritis.
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PMID:Gender-related influences on the development of chronic graft-versus-host disease-induced experimental lupus nephritis. 844 66

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.
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PMID:Cytokine gene expression in mice undergoing chronic graft-versus-host disease. 848 82

Cells derived from human cord blood instead of bone marrow were recently used for transplantation. However, several questions concerning the potential of this source of cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce graft-versus-host disease (GVHD) remain unanswered. We used newborn blood (NBB) cells from B10.D2 mice to engraft lethally irradiated (DBA/2 x B10.D2)F1 recipients incompatible for multiple non-H-2 antigens. The median volume of NBB collected from one mouse ranged between 40 and 50 microliters and the number of nucleated cells was approximately 4-5 x 10(5) per sample. We first established that NBB contains around 10-20% of stem cells (SCA-1+) and 30% of CD4+CD8+ Thy-1+ immature T cells. The injection of blood pooled from one to three newborn mice resulted in engraftment of 71%-86% of F1 recipients that survived more than 100 days. Long-term surviving mice exhibited mixed chimerism (approximately 69% of cells of donor origin) 2-4 months after transplantation, and clinical signs of GVHD across minor histocompatibility Ags (mHAgs) were never observed. Additionally, mixed lymphocyte reaction and cytotoxic assay responses of those mice against host antigens were undetectable, while reactivity against unrelated H-2 Ag was normal. The establishment of host-specific tolerance in NBB engrafted mice was confirmed by in vivo transfer experiments. In conclusion, NBB cells reconstituted the lymphohematopoietic system of lethally irradiated mice without inducing GVHD. However, the question of the presence of an active antileukemic effect remains to be answered.
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PMID:Newborn blood used as a source of donor cells in a murine model of transplantation across non-MHC antigens. 859 73

The suppressed lymphocyte proliferative responses characteristic of graft-versus-host disease (GVHD) are due, in part, to production of nitric oxide (NO). In order to more fully elucidate the role of NO during GVHD, an NO synthesis inhibitor, aminoguanidine (AG), was administered to unirradiated (C57BL/6J X DBA/2J)F1 mice injected with 5 X 10(7) C57BL/6J splenocytes. Administration of AG resulTed in abrogation of the elevation in serum NO2- + NO3- levels characteristic of GVHD. A significantly increased percentage of splenocytes of host phenotype (H2b/d, B220+, and THY1.2+) and a significantly higher hematocrit value were detected in GVHD animals receiving AG therapy. Additionally, the Con A-induced proliferative response of splenocytes obtained from GVHD mice receiving AG therapy was increased compared with the responses of splenocytes from animals that did not receive AG therapy. Parameters not affected by AG therapy included NO synthesis by recovered peritoneal macrophages, donor antihost cytolytic activity in splenocyte populations, serum GM-CSF levels and long-term engraftment of donor cells. These data indicate that NO may play a role in the destruction of both lymphoid and erythroid host tissue as well as the reduced lymphoproliferative responses associated with the acute phase of GVHD.
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PMID:Bystander injury of host lymphoid tissue during murine graft-verus-host disease is mediated by nitric oxide. 861 Mar 89

Cells derived from human cord blood were recently used instead of bone marrow (BM) for transplantation. However, several questions concerning the potential of these cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce a graft-versus-host disease (GVHD) remain unanswered. Here we used newborn blood (NBB) cells from B10.D2 mice to engraft lethally irradiated (DBA/2 x B10.D2)F1 recipients incompatible for multiple non H-2 antigens. Few mature T cells were found in NBB as in adult BM and both contain around 10% to 20% SCA-1+ pluripotent progenitor cells. Yet numerous immature CD4+CD8+ TCR alpha/beta low Thy-1high T cells were present in NBB. In contrast, adult peripheral blood (PB) exhibits a mature T-cell phenotype and contains few progenitor cells. The injection of blood pooled from one to three newborn mice resulted in the engraftment of 71% to 86% of F1 recipients, which survived more than 100 days without clinical signs of GVHD. The injection of BM leads to 100% survival whereas the injection of adult PB resulted in rapid mortality, both without signs of GVHD. In NBB-engrafted F1 surviving mice, T-cell reconstitution preceded B-cell reconstitution, and the degree of donor cell chimerism increased progressively with time. Additionally, 2 to 4 months after transplantation, T cells from these mice were tolerant to host non H-2 antigens but kept reactivity against third-party Ags. Host specific tolerance in NBB-engrafted F1 mice was confirmed by in vivo transfer experiments. In conclusion, NBB cells were able to reconstitute the lymphohematopoietic system of lethally irradiated adult mice without inducing GVHD against incompatible non H-2 antigens. Thus, this experimental model in vivo may be relevant to the human cord blood transplantation.
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PMID:Newborn blood can engraft adult mice without inducing graft-versus-host disease across non H-2 antigens. 861 30

We have investigated graft-versus-leukaemia (GVL) effects after allogeneic bone marrow transplantation (BMT), using three murine leukaemia models, A20 (B lymphocytic), WEHI-3 (myelomonocytic) and PU5-1R (myeloid). Injection of leukaemia cells in a high number (10(6) cells) into syngeneic Balb/c mice (H-2d) invariably led to death with a median survival time of 22 d (A20), 18 d (WEHI-3) and 45 d (PU5-1R). A lower tumour load of A20 (5 x 10(5) cells) was used in some experiments resulting in a leukaemic death rate of 94%. Lethal total-body irradiation followed by syngeneic BMT prolonged survival (P<0.05) for animals bearing the leukaemia A20 and WEHI-3 but was unsuccessful for animals injected with cells from the monocytic leukaemia PU5-1R. Graft-versus-host (GVH)-nonreactive marrow of (C57 x Balb/c)F1 mice (H2bxd) exerted a significant GVL-effect with reduced relapse rate and improved survival in mice receiving the leukaemia cell line A20. In animals with low tumour load a significant reduction of the relapse rate from 82% following syngeneic BMT to 47% following allogeneic, GVH-nonreactive BMT could be achieved. Depletion of natural killer (NK) cells from the GVL-reactive semi-allogenic bone marrow graft enhances the relapse rate of the leukaemia A20 to 65%. In mice bearing the leukaemias WEHI-3 or PU5-1R allogeneic GVH-nonreactive BMT did not improve survival compared to syngeneic BMT. Transplantation of GVH-reactive bone marrow from DBA mice (MHC identical to Balb/c, minor difference) caused only a limited and insignificant reduction of relapse rate for animals with the leukaemia A20. These in vivo data are in close correlation with in vitro natural killer cell (NK) activity of the donor strains against the respective leukaemia targets. Depletion of NK cells from the GVL-reactive (C57 x Balb/c)F1 bone marrow resulted in a significant loss of GVL activity. We conclude that NK cells are involved in graft-versus-leukaemia effects independent of graft-versus-host disease (GVHD).
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PMID:Graft-versus-leukaemia activity can be predicted by natural cytotoxicity against leukaemia cells. 863 41

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