Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Interleukin 2 induces interferon alpha/beta production in mouse bone marrow cells. 310 59

Highly purified populations of L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to cause lethal GVHD in six different H-2-compatible, multiple minor histocompatibility antigen-different murine strain combinations. In four of these combinations (C3H.SW----B6, DBA/2----B10.D2, B10.BR----CBA, and B10.S----SJL), lethal GVHD appeared to be caused almost entirely by Lyt-2+ cells; the injection of L3T4+ cells resulted in low mortality even when these cells were presensitized to the recipient antigens. In the remaining two combinations (B10.D2----DBA/2 and B10.D2----BALB/c), L3T4+ T cells were able to cause a high incidence of GVHD and were more potent than the Lyt-2+ cells. The implications of these findings are discussed.
 ...
PMID:Variable capacity of L3T4+ T cells to cause lethal graft-versus-host disease across minor histocompatibility barriers in mice. 310 46

Galactose oxidase was labelled onto the surface of mitomycin-C treated splenic lymphocytes from BALB/C mice (H-2d, Mlsb). Mouse splenic lymphocytes from DBA/2 (H-2d, Mlsa) mixed with the galactose oxidase labelled BALB/C lymphocytes allowed DBA/2 cells which recognized the Mlsb on the BALB/C cells to make direct contact with the galactose oxidase labelled BALB/C cells. By adding galactose, sodium iodide and catalase to the mixture, the contacting stimulator cells will generate hydrogen peroxide in the vicinity of the contacting responder cells and the iodine ions will exert a toxic effect on the responder cells while non-specific cytotoxicity was prevented by catalase. When fresh mitomycin-C treated BALB/C lymphocytes were added to the cell mixture, the mixed lymphocyte response against BALB/C cells by the treated DBA/2 lymphocytes was abolished. On the other hand, when fresh mitomycin-C treated lymphocytes from C57BL/6 mice (H-2b, Mlsb) were mixed with the treated DBA/2 cells, the mixed lymphocyte response against C57BL/6 cells by the treated DBA/2 lymphocytes was partially retained. Therefore, although some non-specific cytotoxicity was present, a method to deplete specific T-lymphocytes that recognize major histocompatibility antigen from a mixed cell population while maintaining immune responsiveness towards other antigens was developed. This method may have a beneficial effect on the control of post-transplant immunity and may be used as a prophylaxis of graft-versus-host disease.
 ...
PMID:A trial of alloreactive T-cell depletion using biotinylated galactose oxidase for the prevention of acute graft-versus-host diseases. 325 39

Systemic lupus erythematosus-like graft-versus-host (GVH) disease was induced in 10-week-old male (C57BL/10 X DBA/2) F1 mice by the intravenous injection of spleen and thymus cells (2:1) from 10-week-old male DBA/2 mice. GVH mice were bled at regular intervals 1 month after injection. Antibody to nuclear antigens (ANA) were detected by immunofluorescence using HEp-2 cells as substrate, and antibody to histones and DNA were detected by enzyme-linked immunosorbent assay (ELISA). The titer and frequency of ANA were found to relate directly to the number of donor cells injected. In order to determine the spectrum of ANA in GVH disease, mice were reinjected with optimum cell numbers (120 X 10(6], and splenocytes from two mice with high titer ANA were fused to mouse myeloma cell line P3/X63Ag8.653. Hybridomas were analyzed for ANA by immunofluorescence and ELISA. Sixty-eight clones were found which secreted ANA. Of these, 59% produced antibody to double-stranded DNA, single-stranded DNA, and/or histones and the remainder gave a variety of nuclear immunofluorescence patterns including speckled, homogeneous, nuclear matrix, and nucleolar. This study indicates that GVH disease provides an excellent source of splenocytes for the production of ANA-producing hybridomas as well as a model for the study of autoimmunity.
 ...
PMID:Monoclonal autoantibodies to nuclear antigens from murine graft-versus-host disease. 349 80

(C57BL/6 X DBA/2)F1 mice undergoing the graft-vs-host reaction (GVHR) produce autoantibodies after the injection of DBA/2 lymphoid cells. The anti-nuclear antibodies, including anti-poly (ADP-ribose) and anti-extractable nuclear antigens (ENA), in the sera of the autoimmune GVH F1 mice were investigated. Antibodies to double-stranded DNA, single-stranded DNA and ENA were predominantly IgG. In contrast, the autoantibodies to poly(ADP-ribose) were both IgG and IgM, although the former was predominant. These autoantibodies induced by the GVHR showed similar cross-reactivities with a number of nucleic acids to the monoclonal and some serum antinuclear antibodies derived from mice or humans with systemic lupus erythematosus (SLE). These results support the idea that GVH F1 mice are a good model of human SLE.
 ...
PMID:Specificity of anti-nuclear antibodies induced in F1 mice undergoing the graft-vs-host reaction: isotypes and cross-reactivities. 349 93

A minor (non-H-2) graft-vs.-host reaction (GVHR) was induced in adult irradiated (DBA/2 X B10.D2)F1 mice by hematopoietic parental B10.D2 cell grafts. Syngeneic (F1) cell transplantation was performed as control. In one set of experiments T4 plasma level (enzyme linked immunosorbent assay) was systematically followed up in individual GVHR and control mice. Compared to the control, GVHR triggered off a significant and sustained decrease of T4 plasma level. In another set of experiments, TSH plasma levels (RIA) were measured in killed animals. GVHR induced an early elevation of plasma TSH. In a third set of experiments, mice undergoing GVHR received daily injections of L-T4 (0.03, 0.15, or 0.3 microgram/mouse). Compared to the control (saline injected) GVHR mice, T4 supply did not improve GVHR state. No positive effect of the high dose and rather a negative effect of both lower doses especially on glucose plasma concentration, were observed. All these data suggest that thyroid gland is primarily and very early involved in the onset of the GVH disease.
 ...
PMID:Endocrine involvement in minor (non-H-2) graft-versus-host reaction in mice. Early and primary thyroid failure. 356 37

In the H-2 compatible (but minor loci-incompatible) BALB/c-DBA/2 strain combination (both H-2d), intravenous injection of 1.3 X 10(7) BALB/c spleen cells from virgin females into DBA/2 newborn mice less than 18 h old does not result in a significant lethal graft-versus-host reaction (GVHR). A strong GVHR (79% lethal) is induced if the BALB/c donors have been preimmunized to DBA/2. Spleen cells from BALB/c mice pregnant by DBA/2 males are also able to induce a significant, but weaker, GVHR (16% lethal) indicating a cellular priming to paternal antigens by gestation. A significant difference exists between anti-DBA/2 GVH reactivity of spleen cells from primiparous (22% lethal) and multiparous (9% lethal) allopregnant BALB/c mice, indicating that the allogeneic boosters of successive allogestations act more on the target-protective side of immunity than on the target-aggressive one. Sera from allopregnant mice (BALB/c X DBA/2) inhibit the GVHR induced by their own cells, while sera from isopregnant ones (BALB/c X BALB/c) have no effect. Thymectomy performed at 6-wk of age, six weeks before gestation did not significantly modify the maternal reactivity. A similar priming by allogestation in the same strain combination was found for local GVHR (induced in adult F1 hybrids) resulting in higher (+132%, P less than 0.005) stimulation indices and seen to be specific for the paternal strain, the indices induced by the same cells being lower (-35%, P less than 0.05) compared to that induced by cells from virgin BALB/c, when injected into irrelevant F1 hybrids (BALB/c X CBA).
 ...
PMID:Maternal alloimmune reactions towards the murine conceptus and graft-versus-host reaction (GVHR). I. Priming for anti-paternal GVHR by gestation. 374 77

Gestation can induce a priming for a GVHR towards paternal strain antigens, although this priming is significantly lower than the one induced by experimental immunization. A role has been sought for placental substances in decreasing this priming through immunomodulation. BALB/c (H-2d) spleen cells do not usually induce a systemic, lethal GVHR in DBA/2 (H-2d) newborn mice except when the donors are preimmunized with DBA/2 cells. Placental extracts (as well as RPMI medium or liver extracts used as controls) were added to DBA/2 cells injected into BALB/c mice used as cell donors for GVH induction. The latter's spleen cells, harvested on day 6 after immunization, were used for systemic and local GVHR. In the systemic assay (lethal effect on DBA/2 newborn mice injected i.v. with BALB/c spleen cells) a significant protection was observed. In the local assay (popliteal lymph node assay in F1 hybrids injected with BALB/c spleen cells into the foot-pad) a highly significant inhibition of priming was detected in recipients injected with spleen cells from placental extract-treated donors. The stimulation index was even lower than that obtained with unprimed BALB/c spleen cells. The same type of local GVHR in (CBA/Ca X A/J) F1 hybrids injected with CBA cells led to similar results. In both situations (systemic and local GVHR) the observed inhibition was found to be specific to the priming cell strain. These results support the working hypothesis that placental substances are able to modify the systemic response of an organism towards both H-2 and non-H-2 alloantigens.
 ...
PMID:Maternal alloimmune reactions towards the murine conceptus and graft-versus-host reaction (GVHR). II. Inhibition of priming by placental extracts. 374 78

Previous work has established that a disease resembling systemic lupus erythematosus (SLE) can be induced in certain nonirradiated F1 mice undergoing a suitable graft-versus-host reaction (GVHR), e.g., (C57BL/10 X DBA/2)F1 mice injected with DBA/2 T cells. Here, we studied the antibody responses of such autoimmune graft-versus-host F1 mice to exogenous antigens, i.e., sheep erythrocytes, trinitrophenyl keyhole limpet hemocyanin, and levan. We found that primary antibody responses, in particular of IgG isotype, to the T-dependent antigens, sheep erythrocytes, and trinitrophenyl keyhole limpet hemocyanin were strongly suppressed during the entire observation period. Secondary anti-sheep erythrocyte responses, however, were normal, although the peak response was delayed for about 3 days. In contrast to the long-lasting depression of responses to T-dependent antigens, primary antibody responses to the T-independent antigen levan were depressed only at an early stage (i.e., week 2) of the graft-versus-host reaction. In spite of their depressed antibody responses to exogenous antigens, the graft-versus-host F1 mice showed increased numbers of spleen cells spontaneously secreting IgG, and produced IgG autoantibodies characteristic of systemic lupus erythematosus. Mixing experiments performed in vitro with cultures involving graft-versus-host spleen cells revealed that the decreased antibody formation cannot be attributed to suppressor T cells nor to a defect in helper T-cell function. Instead, the mechanism of decreased immune reactivity in SLE-like GVHR seems to operate at the level of B cells. Parallels between the decreased immune reactivity observed in lupus-like GVH disease and that described in human SLE as well as in spontaneously arising murine SLE are discussed.
 ...
PMID:Depressed antibody responses to exogenous antigens in mice with lupus-like graft-versus-host disease. 382 58

We asked the question whether or not the Lyb-3+5+ B cell subset, which is lacking in CBA/N immune defective mice, is required for the lupus-like autoantibody formation caused by graft-vs-host reaction (GVHR). (CBA/N X DBA/2)F1 male defective mice injected with DBA/2 T cells produced IgG autoantibodies to the same extent as did nondefective F1 mice suffering from GVHR. Although a very small number of DBA/2 B cells might have contaminated the T cell inocula, it was shown that these were B cells of the defective F1 mice that produced autoantibodies during the GVHR. This was demonstrated by detecting autoantibodies carrying an immunoglobulin allotype of the F1 recipient. Furthermore, the defective F1 male mice injected with CBA/N lymphoid cells, which were lacking Lyb-3+5+ B cells, also produced autoantibodies. Isotype analysis of antinuclear antibodies revealed that some of them belonged to IgG3 isotype. It was concluded that the ontogenically late-appearing B cell subset is not required for GVH autoimmunity.
 ...
PMID:The Lyb-3+5+ subset of B cells is not required for lupus-like autoantibody formation caused by graft-vs-host reaction. 387 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>