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)

We have used a cell-wall-deficient mutant of Escherichia coli (E coli J5) to study the effect of active and passive immunization against bacterial endotoxin (ET) in a murine model of acute graft-versus-host disease (GVHD) induced by minor histocompatibility antigens. C57BL/B6 (H-2b) mice were irradiated and grafted with 1 X 10(7) anti-Thy-1.2 and complement-treated bone marrow cells and 5 X 10(7) spleen cells from LP/J (H-2b) donors. Groups of mice were immunized against J5--either actively immunized with killed J5 cells or pure J5 lipopolysaccharide or passively immunized with rabbit anti-J5 antiserum (R alpha J5). Controls included irradiation controls, negative controls (conventional mice grafted with depleted bone marrow only), positive controls (conventional mice grafted with bone marrow and spleen cells), and mice passively immunized with normal rabbit serum (NRS). Positive control mice developed GVHD and all died by day +77. Active immunization partially protected against the rapid weight loss due to GVHD (P less than 0.05) but mice had an earlier onset of GVHD (P less than 0.05) and a shortened survival after onset (P less than 0.05). Median survival time (MST) and overall survival were unchanged. Passive immunization with R alpha J5 delayed death (P less than 0.01), increased MST (P = 0.01), increased overall survival (P less than 0.01), and protected against weight loss (P = 0.01). NRS had no beneficial effect.
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PMID:Effect of immunization with Escherichia coli J5 on graft-versus-host disease induced by minor histocompatibility antigens in mice. 330 49

Studies were conducted to determine whether a functional B cell defect occurred in the bone marrow of mice experiencing a GVH reaction (GVHBM). GVH reactions were induced in AxCBA F1 adult mice by an injection of A strain lymphoid cells. The GVH reaction was confirmed by immunosuppression and thymus histology. At various intervals after GVH induction, GVHBM was tested for its ability to restore B cell function in adult thymectomized irradiated mice reconstituted with normal thymocytes. GVHBM cells obtained seven days after GVH induction restored but slightly the plaque forming cell (PFC) response to sheep erythrocytes and the mitogen response to lipopolysaccharide (LPS). GVHBM cells obtained 10 days or later failed to reconstitute the PFC or LPS responses. GVHBM cells suppressed neither the T or B cell function of normal spleen cells nor the LPS mitogen response of normal bone marrow cells. In addition, the splenic colony-forming units (CFU-s) in GVHBM were slightly decreased by day 10 after GVH induction and markedly depressed by day 22 after GVH induction. These results suggest that the GVH reaction may affect two different events in B cell differentiation. The early decrease in functional B cells that occurs before there is any change in the CFU-s population suggests a direct effect on B cell production, whereas the later absence of functional B cells could be due to the marked decline in stem cell production (CFU-s).
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PMID:The graft-versus-host reaction and immune function. IV. B cell functional defect associated with a depletion of splenic colony-forming units in marrow of graft-versus-host-reactive mice. 351 85

Much clinical and experimental data suggest that infection and graft-versus-host disease (GVHD) are intimately associated, and that bacterial endotoxin (ET), a potent immunostimulant, influences the severity of GVHD. We have used a cell-wall-deficient mutant of Escherichia coli (E coli J5) to study the effect of active and passive immunization against ET in a murine model of GVHD induced by major histocompatibility antigens. CBA/Ca (H-2k) mice were irradiated and grafted with 1 X 10(7) bone marrow cells from C57BL/B6 (H-2b) donors. Groups of mice were immunized against J5: either actively immunized with killed J5 cells or pure J5 lipopolysaccharide, or passively immunized with rabbit anti-J5 antiserum (R alpha J5). Controls included irradiation controls, negative controls (syngeneic graft), positive controls (conventional mice receiving allogeneic graft), mice immunized with normal rabbit serum, Freund's adjuvant (FA), or human serum albumin (HSA) in FA. Active immunization with J5 exacerbated the effects of GVHD as indicated by increased weight loss (P = 0.002) and earlier death (P = 0.043). In contrast, immunization with HSA protected against weight loss (P = 0.028), and improved survival (P = 0.008). Passive immunization with J5 had no effect. These observations support the hypothesis that ET influences the pathogenesis of GVHD, and provide a useful model for studying the effects of ET in a well-defined immunological system.
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PMID:Influence of endotoxin on graft-versus-host disease after bone marrow transplantation across major histocompatibility barriers in mice. 355 64

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
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PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

Peripheral blood mononuclear leukocytes (cells of marrow donor origin) from 89 patients were collected at various times after allogeneic marrow transplantation, stimulated in vitro by phytohemagglutinin, and assayed for the production of interleukin 2 (IL-2). This was done by testing culture supernatants for their ability to induce proliferation of human lymphoblasts and/or IL-2-dependent cultured murine cytotoxic cells. Supernatants from cultures of patient cells were compared with those of marrow donor cells. Supernatants produced by cells from most short-term marrow recipients (30-101 days postgrafting), regardless of the presence or absence of acute graft-versus-host disease (GVHD), and those from most long-term patients with chronic GVHD (103-1932 days postgrafting) had significantly lower-than-normal IL-2 activity, whereas cells from most long-term marrow recipients without GVHD (353-1934 days postgrafting) had essentially normal IL-2 activity. Additionally, we tested the ability of monocytes from 35 marrow recipients to produce interleukin 1 (IL-1) in response to lipopolysaccharide as compared with monocytes from marrow donors or normal unrelated individuals. IL-1 activity in culture supernatants of patient cells, regardless of the time of testing after marrow grafting and the status of GVHD, was found not to differ from that in supernatants of normal cells. These findings suggest that impaired T cell functions seen in some (but not all) marrow recipients are probably not due to IL-1 but to IL-2 deficiency or to the mechanism that causes IL-2 deficiency.
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PMID:Cellular interactions in marrow-grafted patients. III. Normal interleukin 1 and defective interleukin 2 production in short-term patients and in those with chronic graft-versus-host disease. 388 Sep 62

We examined the effect of a nucleotide-free diet on the immune function of mouse syngeneic bone marrow radiation chimeras. The graft-versus-host disease mortality assay revealed that GVH activity of spleen cells from radiation chimeras fed NFD (RCNFD) was reduced at 6-18 weeks after transplantation as compared with the radiation chimeras fed a control diet (RCCD). When tested 11-18 weeks after transplantation, the proliferative response of RCNFD spleen cells to phytohemagglutinin was significantly reduced at 11 and 13 weeks, the response to pokeweed mitogen (PWM) was significantly reduced at 11, 13, and 15 weeks, and the response to bacterial lipopolysaccharide remained virtually unaffected. At both six and eight weeks after transplantation, RCNFD and RCCD showed comparable numbers of CFUc/femur. RCNFD and RCCD did not differ significantly from each other in body weights or in spleen and bone marrow cellularity at 6-18 weeks after transplantation. These results suggest that dietary nucleotides are important for the normal function of mouse T-lymphocytes.
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PMID:Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide-free diet. 638 8

The present findings demonstrate that a total i.v. transfer of 100 X 10(6) C57BL/6 (B6) parental spleen cells into untreated (C57BL/6 X DBA/2)F1 hybrids (B6D2F1) resulted in acute runting, which was associated with a significantly elevated graft-vs.-host (GVH) index over a one-month period following GVH induction. Furthermore, this B6-induced acute GVH disease was associated with a marked depression of natural killer (NK) cell activity (spleen and peripheral blood) (with or without addition of mouse fibroblast interferon), which correlated with lymphoid cell hypocellularity, prominent splenic extramedullary hematopoiesis (EMH), and parallel depressions of both concanavalin A- and lipopolysaccharide-induced mitogenesis. Significantly increased killing by antibody-dependent cellular cytotoxicity of antibody-coated chicken red blood cells, as well as increased T cell killing of the NK-insensitive cell line P815 (as compared to the significantly decreased killing of the NK-sensitive cell line YAC-1) was also observed in the spleens of this 100 X 10(6) B6-injected F1 group. In marked contrast to this 100 X 10(6) B6-injected acute GVH group, untreated mice injected i.v. with the same or greater numbers of parental DBA/2 spleen cells (100 X 10(6)-150 X 10(6) DBA/2 spleen cells) exhibited a milder and more chronic form of GVH disease, which was not associated with a significant decrease of NK activity. It was of considerable interest that a total i.v. transfer of 50 X 10(6) B6 spleen cells (i.e. one-half of that required to produce acute GVH, markedly depressed NK, and prominent splenic EMH) into B6D2F1 hybrids also resulted in a more chronic form of GVH disease, but was associated with significantly increased levels of NK activity at two weeks post GVH induction.
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PMID:Natural killer activity in (C57BL/6 X DBA/2)F1 hybrids undergoing acute and chronic graft-vs.-host reaction. 664 88

In a previous paper (Gleichmann, van Elven & van der Veen, 1982), it had been reported that, in contrast to lupus like autoantibodies such as anti-DNA, autoantibodies to mouse thyroglobulin (MTg) were not detectable in serum of F1 mice suffering from a lupus like graft versus host disease (GVHD) (GVH F1). In the present paper, possible explanations for this restricted autoantibody formation during the potent allogeneic stimulation were investigated. The main question was whether the natural level of circulating MTg was too low to induce the formation of anti-MTg antibodies in GVH F1 mice. Existence, in the F1 mice studied, of B cells capable of producing anti-MTg antibodies was demonstrated by injection of lipopolysaccharide (LPS) and exogeneous MTg. However, MTg injected into various F1 mice at the onset of the GVH reaction (GVHR) failed to overcome the lack of antibody formation to MTg even though the GVHR led to a severe lupus like disease. Furthermore, adult thymectomy (ATx) of either the recipients, the donors, or both also did not break tolerance to MTg during the GVHR, irrespective of administration of exogeneous MTg. Thus, neither intravenous injection of MTg nor ATx, designed to remove T suppressor (TS) cells, is adequate to enable an autoantibody response to MTg during lupus like GVHD. Hence, the non-specific T cell help that causes lupus like GVHD seems to be intrinsically insufficient to trigger the Tg reactive B cells. We suggest that globular proteins, such as Tg, require specific T cell help. In the presence of only non-specific T help, self-antigens such as DNA seem to be more apt than globular proteins to provide an effective signal 1 to the corresponding autoreactive B cells.
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PMID:Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft versus host disease in mice. 670 66

The crucial role of macrophages in the generation of the rat graft-versus-host reaction (GVHR) was investigated in normal and macrophage-depleted F1 hybrid rats. The addition of exogenous macrophages, colloidal carbon, or lipopolysaccharide (LPS) resulted in a great augmentation of GVH reactivity of parental lymph node cells in normal F1 hybrid rats. Uptake of foreign materials by F1 macrophages exerts a biphasic action on the GVHR, activating or blocking the biological activity. This depends on the time of injection of foreign materials. To define the extent of macrophage dependence in the GVHR, the additive effect of exogenous macrophages on the reaction was investigated in F1 hybrid rats depleted of effective macrophages and lymphocytes, which had received preliminary host irradiation and colloidal carbon injection. In F1 hybrids depleted of macrophages and given injections of parental lymph node cells depleted of macrophages, the addition of exogenous F1 macrophages resulted in a much higher reaction than did lymphocytes alone. The data suggest that macrophage-induced augmentation of the reaction may be a reflection of the regulatory function of macrophages in the cellular interactions between parental GVH-reactive lymphocytes and alloantigen-bearing host cells in vivo.
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PMID:Augmenting effect of exogenous macrophages on the rat graft-versus-host reaction in F1 hybrids depleted of macrophages. 721 Jan 47

We have recently shown that donor CD4-enriched cells of Th2 cytokine phenotype, generated by treating mice in vivo with a combination of interleukin-2 (IL-2) and IL-4, prevent lipopolysaccharide-induced, tumor necrosis factor-alpha-mediated lethality during graft-versus-host reaction. To assess the potential regulatory role of such Th2-type cells in lethal graft-versus-host disease (GVHD) and graft rejection, we used a fully allogeneic murine transplant model using sublethally irradiated hosts (B6-->C3H, 500 cGy). Such recipients generated a strong host-versus-graft response, as reflected by their ability to reject T-cell-depleted inocula. The administration of T-cell-containing donor whole spleen inocula resulted in alloengraftment, but such recipients developed lethal GVHD. However, mice receiving sequential donor whole spleen (day 0) and CD4-enriched, Th2-type (day 1) populations engrafted, and had prolonged survival with protection from histologically defined tissue injury associated with GVHD. The findings in this fully allogeneic model thus extend our previous observations and indicate that the transfer of donor Th2-type cells may be an important strategy for regulating GVHD. Furthermore, the sequential "Th1(-)-->Th2-type" donor cell transfer described in this report represents a novel approach for abrogating graft rejection with concomitant control of GVHD and illustrates the importance of kinetics in the interaction of functionally distinct donor T-cell populations.
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PMID:Donor CD4-enriched cells of Th2 cytokine phenotype regulate graft-versus-host disease without impairing allogeneic engraftment in sublethally irradiated mice. 794 9

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