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)

The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cycloporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell.
 ...
PMID:Biological effects of cyclosporin A: a new antilymphocytic agent. 0 69

In vitro experiments were carried out to investigate the immunosuppressive efect of different populations of spleen cells obtained from animal experiencing a graft-versus-host reaction (GVHR). To induce the GVHR, parental lymphoid cells were injected into adult F1 hybrid mice. GVHR-activated spleen cells (GVH-sc) taken at different times post-GVHR induction were separated into adherent and non-adherent fractions and treated with anti-theta serum plus complement. The different types of GVH-SC were added to either parental (donor-type) of F1 (host-type) normal spleen cells and cultured with sheep erythrocytes in a modified Marbrook chamber. It was found that both adherent and non-adherent 10-day GVH-SC significantly inhibited the plaque-forming cell response of F1 normal spleen cells but not that of parental normal spleen cells. Significant suppression of the parental response was observed following the addition of 15-day GVH-SC or anti-theta treated adherent and non-adherent 7-day GVH-SC. The results suggest that the non-specific immunosuppressive effect of GVH-SC is mediated by GVHR-activated macrophages and B lymphocytes found in the anti-theta treated adherent and non-adherent fractions of the GVH-SC suspensions respectively.
 ...
PMID:Evidence for two types of non-specific suppressor cells activated by the graft-versus-host reaction in mice. 2 11

Following the i.c. inoculation of dengue type 2 virus (DV) the spleen weight of infected mice was reduced, as was the proportion of cells killed by ATS and complement (T lymphocytes) in spleen-cell suspensions. In DV-infected mice the mean haemolysin titre, 16 days after i.p. inoculation of 4 x 10(8) SRBC, was 47 compared with 406 in normal mice and spleen cells from DV-infected mice produced significantly reduced direct GVH reactivity in Parker strain (PS) infant mice. Adoptive transfer of spleen cells obtained from mice given three weeks i.p. doses of DV or a single i.c. dose, suppressed antigen-specific antibody secretion as detected by Jerne plaque technique. This suppression was abrogated by pretreating the transferred cells with ATS and complement. Thus DV selectively depletes T-lymphocyte subpopulations responsible for helper and effector functions and spares suppressor T cells in the spleen of infected mice.
 ...
PMID:Differential depletion of T lymphocytes in the spleen of dengue virus-infected mice. 3 5

We have previously shown that two distinct mouse placental fractions (PF) are potent immunomodulators in vivo. A 40 kDa PF induces a marked decrease of plaque forming cell (PFC) responses, while a 60 kDa PF increases them. Both effects are specific for the priming antigen. In the present study, these two PF are assayed on a cell-mediated response to allogeneic cells, i.e. in a local graft-versus-host reaction (LGVHR). Mice were primed with allogeneic cells in the presence of various amounts of the 40 kDa or 60 kDa PF, or liver extract (LE) as control. Six days later, their spleen cells were injected into the footpads of F1 recipients. Precise dose-response curves were established and the kinetics of the GVH response were carefully followed. Parallel with the modulation of PFC responses, the 40 kDa PF caused a potent inhibition of the LGVHR, while the 60 kDa PF greatly enhanced it. Both effects were specific for the alloantigens injected with the PF. Furthermore, we showed that these modulations were observed whatever the intensity of the GVH reaction, which varied according to the number of primed spleen cells transferred. This report also demonstrates that these PF can be greatly enriched by passage over affinity columns made of insolubilized lectins. The 40 kDa PF is retained on and can be eluted from columns of insolubilized concanavalin A (Con A) or wheat germ agglutinin (WGA), which indicates that it is a glycoprotein. Conversely, the 60 kDa PF does not bind to any of the above lectins and is probably not a glycoprotein. This biochemical purification step is also a good procedure for obtaining an even cleaner separation of the two fractions from each other. Thus, this paper demonstrates that both PF have important regulatory properties on specific cellular immune responses.
 ...
PMID:Antigen-specific modulation of graft-versus-host reactions by two distinct placental factors. 246 25

Graft-versus-host disease (GVHD) and states of immune reconstitution in allogeneic chimera mice across minor histocompatibility antigens were analyzed in excess of 9 months after injecting AKR/JSea (AKR) spleen cells into irradiated C3H/HeSlc (C3H) mice. When T cell-depleted AKR spleen cells were used as inoculum cells, neither graft failure nor GVHD was seen for 9 months postgrafting in the C3H mice irradiated with 660 rad or more. In an AKR - C3H (850 rad) model, Thy1.1+ or L3T4+ T cell depletion from donor AKR spleen cells abolished both acute and chronic GVHD in lethally irradiated C3H mice. Lyt2+ T cell depletion, however, resulted in acute and chronic GVHD in more than half of the recipient C3H mice. Moreover, actual existence of donor (AKR)-type T cells with L3T4 phenotype, but not Lyt2 phenotype, was always observed in the spleen of the C3H mice suffering from acute GVHD. In addition, the C3H mice that were irradiated with 850 rad, grafted with AKR spleen cells depleted of Lyt2.1+ T cells, escaped from acute GVHD and survived for more than 10 mo postgrafting, showed impaired activities of immune responses such as delayed footpad reaction to sheep red blood cells, antibody production tested by IgM plaque forming cells and reactivity to an intracellular bacterium. Listeria monocytogenes as compared with the C3H mice reconstituted with syngeneic C3H spleen cells or Thy1.1+ or L3T4+ T cell-depleted AKR spleen cells. These results suggest that L3T4+ T cells, rather than Lyt2+ T cells, contained in the grafted cells not only cause acute GVHD but also a long-term immunodeficient state (chronic GVHD) in recipient mice in the H-2-identical murine combinations examined here.
 ...
PMID:The effect of T cell depletion from spleen cell allografts on graft-versus-host disease and long-term immune reconstitution in H-2 haplotype-identical murine combinations. 251 51

Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth. The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection. Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications. One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT. Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis. Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth. Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium. Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus. There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse. 264 92

We have been investigating the effects of polyinosinic:polycytidylic acid (pI:C), an interferon inducer, on the graft-versus-host reaction. We have previously shown that pI:C treatment of C57BL/6xAF1 (B6AF1) recipient mice immediately before injection of C57BL/6 (B6) parental lymphocytes inhibited the immuno-suppression and pathological changes normally caused by the GVH reaction, by a mechanism apparently identical to that seen in F1 hybrid resistance (HR) to hematopoietic grafts. We now demonstrate that delaying pI:C treatment by as little as 48 hr produces the opposite effect. Treatment of recipient B6AF1 mice at different days after transfer of parental lymphocytes induced a marked increase in the severity of the GVH reaction, as measured by a decreased plaque-forming cell response to sheep erythrocytes; decreased proliferative response to the T and B cell mitogens PHA, Con A, and LPS; increased pathological changes in both lymphoid and nonlymphoid tissues; and increased GVH-associated mortality. This effect is unrelated to HR, as pI:C was able to augment the severity of the GVH reaction when A strain cells were injected into AxCBAF1 recipients, which do not manifest HR. Early pI:C treatment (1 and 2 days after parental cell transfer) increased the severity of the GVH reaction much more than later pI:C treatment (7 and 8 days after parental cell transfer). This observation, along with the demonstration of altered pathology in GVH mice treated with pI:C, suggests that the effect of pI:C is not mediated through a direct suppressive effect of IF on the cells responding in either the PFC or mitogen assays, but rather by the ability of IF to activate or suppress mechanisms involved in the development of GVH-induced alterations.
 ...
PMID:The effects of polyinosinic:polycytidylic acid on the graft-versus-host reaction. III: Increased severity of the reaction with delayed pI:C treatment. 274 89

Graft-versus-host disease was studied on the 10th and 14th postoperative days in Lewis x Brown Norway F1 rats (LBN-F1) receiving Lewis accessory heterotopic intestinal allografts. LBN-F1 isograft recipients and LBN-F1 rats were used as controls. The rats were injected with sheep erythrocytes five days before sacrifice. Rats with graft-versus-host disease had progressive loss of the normal architecture of the lymphoid organs. Skin, liver, colon, and salivary glands were infiltrated with immunoblasts and had patchy areas of necrosis. Concurrent with these changes, there were significant, progressive reductions in hemolytic titers, splenocyte plaque-forming counts, viable splenocytes, and the in-vitro splenocyte response to stimulation with concanavalin A. Graft-versus-host disease following intestinal allotransplantation damages the host's lymphoid tissues, producing profound immunosuppression. This finding has implications for clinical intestinal transplantation.
 ...
PMID:Graft-versus-host disease associated with intestinal transplantation in the rat. Host immune function and general histology. 279 6

Spontaneous plaque-forming cells (S-PFC) were followed in 67 bone marrow transplantation (BMT) recipients and 41 controls. Patients with no acute graft-versus-host disease (GVHD) had decreased IgA and IgM S-PFC up to 7 weeks after BMT compared with controls. Patients with acute GVHD had increased IgG, IgA, and IgM PFC compared with controls and patients without GVHD during the first 4 weeks after BMT. The maximum number of S-PFC increased with increasing severity of acute GVHD. However, at diagnosis of GVHD there was no difference in S-PFC in patients who resolved their GVHD or in those who developed more severe GVHD. After 6 weeks, patients with acute GVHD had significantly decreased IgA and IgM S-PFC compared with normal. No major changes in S-PFC were induced during various infections. However, a patient who developed urticaria had a dramatic increase in S-PFC. Patients studied more than a year after BMT had reduced IgM S-PFC compared with controls. It is concluded that S-PFC are reduced after BMT, but markedly enhanced during acute GVHD.
 ...
PMID:Polyclonal antibody secretion during acute graft-versus-host disease. 282 43

This investigation uses different polyclonal activators of in vitro immunoglobulin production to elicit immunoregulatory profiles of B cells, T cells, T4 cells, and T8 cells from 25 recipients (13 with and 12 without chronic graft-v-host disease [GVHD] ) after HLA-identical marrow transplantation for aplastic anemia or hematologic malignancy. Pokeweed mitogen, Epstein-Barr virus, herpes simplex type 1 virus, and tetanus toxoid were used to induce immunoglobulin production as measured by a plaque assay. Multiple defects in the various lymphoid subsets were found in both groups of patients. There was defective b cell function, lack of T cell or T4 cell subset helper activity, and increased T cell, T4 cell, or T8 cell suppressor activity after stimulation with the various activators. Inconsistent B, T, T4, and T8 cell functions in the marrow graft recipients provide evidence for (a) different functional groups of cells within each subset responsive to different polyclonal activators; (b) a spectrum of immune capabilities within each phenotype lineage; (c) different patterns of immune reconstitution for each lymphocyte subset after marrow grafting; and (d) chronic GVHD altering recovery of in vitro functional responses to the different polyclonal activators.
 ...
PMID:The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting. 298 45


1 2 3 4 Next >>