Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

In DA rats grafted with PVG hearts a short course of cyclosporine induces a state of specific unresponsiveness. In animals with grafts surviving greater than 75 days, the W3/25+ (CD4+) subset loses its capacity to mediate rejection of PVG but not third-party heart grafts when transferred into irradiated DA hosts. In this study we examined whether there was an associated change in the capacity of peripheral lymphoid T cell subsets from unresponsive animals to induce graft versus host (GVH) reactivity. First we demonstrated that there is synergy between naive CD4+ and CD8+ cells in the popliteal lymph node PLN assay, but that alone, only CD4+ and not CD8+ cells proliferate. Unfractionated and CD4+ cells from unresponsive animals produced similar PLN enlargement in both donor-specific (DAxPVG)F1 hosts and third-party (W/FxDA)F1 hosts. This enlargement was comparable to that produced cells from naive and specifically sensitized hosts. MRC OX8+ cells from both unresponsive and naive hosts did not produce PLN enlargement unless large numbers were injected; small numbers of sensitized MRC OX8+ cells produced specific PLN enlargement CD4+ cells from CsA-treated DA did not respond to DA anti-PVG idiotype in an in vivo assay adapted from the host versus graft (HVG) PLN assay. As the PLN assay does not test cells capacity to effect tissue damage, cells from CsA-treated DA rats were tested in a lethal GVHD assay. These cells had the same capacity to induce lethal GVH in irradiated (DAxPVG)F1 and (DAxW/F)F1 hosts. The normal response of cells from unresponsive animals in both proliferative and effector GVH assays shows that cells with the potential to respond to PVG alloantigen and mediate tissue damage are present in unresponsive animals but are prevented from mediating rejection, possibly due to the relatively weak immune stimulus of an organ graft.
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PMID:Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. IV. Examination of T cell subsets in graft-versus-host assays. 197 83

It has been shown that human umbilical cord blood contains stem/progenitor cells comparable in number to that of adult bone marrow. We report here the first successful cases of transplantation of umbilical cord blood cells. The patients were suffering from Fanconi's anemia, complicated by severe aplastic anemia. During pregnancy, it was shown that the mother was carrying a sibling unaffected by the disease and with HLA identical to the patient. Cord blood was collected and frozen in liquid nitrogen at birth. After conditioning with low-dose cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the patients received a cord blood transplant of thawed cells. Three patients have been transplanted without any immediate side-effect. One has not enough follow-up, but two patients are alive and well with complete donor hematologic reconstitution and no chronic graft versus host disease. Potential developments of this technique are an extension of applicability with regard to other diseases that might be transplanted and whether such transplants can be performed in adults. The relative immaturity of the lymphoid system at birth may be advantageous in decreasing the graft versus host reaction if these cells are used in a mismatched transplantation. Cord blood cell banks may be useful for transplants in patients lacking an HLA-identical donor.
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PMID:Transplantation of umbilical cord blood in Fanconi's anemia. 198 24

We have investigated the effects of graft-versus-host disease on T cell differentiation in the murine thymus. We previously reported that GVH-induced thymic dysplasia results in a T cell immunodeficiency associated with a lack of IL-2 production. This deficiency in IL-2 production may be the result of a reduction in the number of L3T4+Lyt-2- IL-2-producing cells or of a functional defect in this population. To test these two alternatives, flow cytometry analysis of L3T4 and Lyt-2 antigen expression on thymocytes along with immunofluorescence microscopy were employed to assess T cell phenotypes in thymuses of GVH mice. GVH reactions were induced by injecting 40 x 10(6) C57BL/6 (B6) or A strain lymphoid cells into C57BL/6xAF1 (B6AF1) mice. Thymocyte populations were quantitated on different days after GVH induction. In the normal thymus, the ratio of L3T4/Lyt-2 single positive cells was greater than 2:1. In contrast, such a ratio was less than 1:1 in the atrophic GVH thymus, owing to a selective reduction in the number of L3T4+Lyt-2- cells. Following cortisone treatment the ratio of L3T4/Lyt-2 single positive thymocytes in normal F1 mice was approximately 3:1, whereas in GVH animals this ratio was reversed (1:2). This reversal was due to a selective reduction in the absolute numbers of L3T4+Lyt-2- cells. In adrenalectomized GVH animals, thymic cortical atrophy was prevented and normal ratios of L3T4/Lyt-2 single positive cells were observed. However, when these animals were treated with cortisone, the L3+T4/Lyt-2- population was more sensitive than was the L3T4- Lyt2+ population, thereby resulting in a 1:2 L3T4/Lyt-2 ratio. These results demonstrate that single positive L3T4 cells are present in the murine GVH thymus, yet they have not acquired cortisone resistance, a trait normally attributed to this mature thymic subset. It appears that the GVH dysplastic thymus can support the differentiation of L3T4+Lyt-2- cells--however, such a thymus is unable to confer cortisone resistance upon this population. Consequently, these cells appear to be eliminated when exposed to corticosteroids in peripheral lymphoid tissue.
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PMID:T cell subsets in the thymus of graft-versus-host immunosuppressed mice. Sensitivity of the L3T4+Lyt-2- subset to cortisone. 198 97

In this preliminary report, our model of VBMT across a semiallogeneic barrier consistently brings about antigen-specific host tolerance with absence of GVHD in the majority of recipients. No immunologic or radiologic intervention was utilized. These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention.
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PMID:Vascularized bone marrow transplantation (VBMT): induction of stable mixed T-cell chimerism and transplantation tolerance in unmodified recipients. 199 Jun 72

A monoclonal antibody recognizing Ly1, the murine homologue of CD5, was labeled with 90Y. In vivo biodistribution studies showed that 90Y-anti-Ly1 selectively localized in lymphoid tissue. Groups of B10,BR mice (H-2k) were lethally irradiated and given major histocompatibility complex-disparate C57BL/6 (H-2b) bone marrow and spleen cells to induce graft-versus-host disease (GVHD). Eight days later, mice with active GVHD were administered a single i.p. injection of 50 microCi90Y-anti-Ly1. Fifty % of these mice were alive 2 months after treatment. Long term (greater than 4-month) survival was significantly higher than in phosphate-buffered saline-treated mice. Survival was slightly improved in groups of mice receiving control irrelevant antibody labeled with 90Y or mice receiving free 90Y. However, survival in these groups was not significantly different from the phosphate-buffered saline-treated control group. The improved survival was supported by data showing improved mean animal weight. An anti-GVHD effect was confirmed by histopathological analysis. Unlabeled anti-Ly1 monoclonal antibody at comparable doses to 90Y-anti-Ly1 was not effective. Animals that died following 50-microCi treatment did not die of radiation toxicity, since all mice receiving 50 microCi 90Y-anti-Ly1 plus syngeneic bone marrow survived. The window of therapy was narrow in our studies, since 100 microCi 90Y-anti-Ly1 did not confer any survival advantage. Animals that did survive long term were studied for evidence of alloengraftment and found to have high levels of circulating donor mononuclear cells. 90Y-Anti-Ly1 localized in the spleen, thymus, liver, kidney and bone marrow but not in the bowel, lung, muscle, or skin. Animals given similar doses of free 90Y, 90Y-anti-Ly1, or labeled irrelevant antibody eliminated free 90Y fastest, followed by 90Y-anti-Ly1 and then labeled irrelevant antibody. Hematological analysis of peripheral blood from 90Y-anti-Ly1-treated mice showed reduction in total WBC counts, absolute lymphocyte numbers, and absolute neutrophil numbers on day 24 after treatment. Myelosuppression recovered by day 38. These findings indicate that Ly1-positive cells are involved in the effector phase of GVHD and that radiolabeled antibodies may be useful as cell-specific probes for studying the GVHD network. 90Y-Anti-Ly1 protected recipients long term from lethal GVHD, and the fact that it had a rather remarkable inhibitory and selective effect on the lymphoid system of mice suggests that these agents may have broader application in the field of transplantation.
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PMID:Radiotherapy in mice with yttrium-90-labeled anti-Ly1 monoclonal antibody: therapy of established graft-versus-host disease induced across the major histocompatibility barrier. 200 72

The transplantation of multiple abdominal viscera, including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas and liver-intestine, is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted en bloc. It is described herein how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component that is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact, which then become the site of two way cell traffic after transplantation. With the use of powerful immunosuppression, such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors, of which insulin has been the most completely studied. An understanding of these various immunologic and nonimmunologic factors combined with more potent immunosuppression that is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera that have resisted such clinical efforts.
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PMID:The many faces of multivisceral transplantation. 202 70

Graft rejection, mixed chimerism, graft-versus-host disease (GVHD), leukemia relapse, and tolerance are interrelated manifestations of immunologic reactivity between donor and host cells that significantly affect survival after allogeneic bone marrow transplantation (BMT). In this report, a mouse model of BMT, in which the donor and host were compatible at the major histocompatibility complex (MHC), was used (1) to examine the interrelationship of pretransplant conditioning and T-cell content of donor BM with regard to lymphoid chimerism and GVHD and (2) to determine how these factors affected graft-versus-leukemia (GVL) reactivity and donor-host-tolerance. AKR (H-2k) host mice were administered optimal or suboptimal total body irradiation (TBI) as pretransplant conditioning followed by administration of BM cells from B10.BR (H-2k) donor mice with or without added spleen cells as a source of T lymphocytes. Transplanted mice were injected with a supralethal dose of AKR leukemia cells 20 and 45 days post-BMT to assess GVL reactivity in vivo. The pretransplant conditioning of the host and T-cell content of the donor marrow affected the extent of donor T-cell chimerism and the severity of GVH disease. GVL reactivity was dependent on transplantation of mature donor T cells and occurred only in complete chimeras. Transplantation of T-cell-deficient BM resulted in the persistence of host T cells, ie, incomplete donor T-cell chimerism, even when lethal TBI was used. Mixed chimerism was associated with a lack of GVL reactivity, despite the fact that similar numbers of donor T cells were present in the spleens of mixed and complete chimeras. In this model, moderate numbers of donor T cells facilitated complete donor T-cell engraftment, caused only mild GVHD, and provided a significant GVL effect without preventing the subsequent development of tolerance after conditioning with suboptimal TBI. In contrast, severe, often lethal, GVHD developed when the dose of TBI was increased, whereas tolerance and no GVH/GVL reactivity developed when the T-cell content of the marrow was decreased.
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PMID:Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance after bone marrow transplantation. 203 33

A rat model of multiorgan transplantation (MOTx) including the liver, pancreas, duodenum, and variable segments of small bowel (SB) was used to ascertain whether graft-versus-host disease (GVHD) could be produced by this procedure. Rats receiving an isogeneic multiorgan transplant (MOT) survived more than 150 days. MOTx was then performed in the Lewis to (Lewis x Brown Norway) LBNF1 semiallogeneic combination, ensuring unidirectional GVHD. En bloc transplantation of the liver, pancreas, duodenum, and entire jejunum provoked lethal GVHD in all animals, and the mean time to recipient death (MT) was 16.5 +/- 0.43. When only one-half of the jejunum was included in the MOT, lethal GVHD similarly occurred in 100% of animals and the MT was 18 +/- 0.86. Finally, when only liver, pancreas, and duodenum were transplanted, the incidence of lethal GVHD was reduced to 50% (P less than 0.1). In those rats that died of GVHD, MT was 16 +/- 0.33. Fifty percent of the rats in this group, however, recovered from a milder form of GVHD and survived more than 150 days. These results demonstrate that MOTx induces GVHD and that the lethality of this process correlates with the inclusion of the SB in the graft and thus, with the overall amount of transplanted lymphoid tissue.
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PMID:Graft-versus-host disease after multiorgan transplantation. 205 73

A 17-year-old boy developed autoimmune pancytopenia in the absence of chronic graft-versus-host disease 170 d after allogeneic bone marrow transplantation (BMT) from his HLA identical brother. The anaemia and thrombocytopenia responded to conventional immunosuppressive treatment, but the neutropenia was refractory to this and to splenectomy and subsequent removal of splenic remnant. Following total lymphoid irradiation the neutrophil count rose to low normal levels but thrombocytopenia and anaemia secondary to marrow hypoplasia required transfusion support. Bone marrow function was finally normalized by an additional transfusion of donor marrow without prior immunosuppressive therapy. We conclude that late onset immune pancytopenia post BMT caused by antibodies of probable donor origin may be life threatening in the absence of chronic graft-versus-host disease.
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PMID:Late onset immune pancytopenia following bone marrow transplantation. 153 5

The inflammatory infiltrate of acute rectal graft-versus-host disease (GVHD) was investigated by indirect immunofluorescence. Twenty biopsies from 11 allogeneic bone marrow transplant recipients were studied in four groups: biopsies before transplantation; biopsies after transplantation without GVHD; biopsies from patients with extra-intestinal GVHD only; and biopsies from patients with intestinal GVHD. Total T cell numbers (CD2+, CD3+) in the lamina propria differed little in the four groups. CD4+ lymphocytes appeared to be decreased in GVHD while CD8+ lymphocytes were significantly increased (p less than 0.01), thus significantly lowering the CD4/CD8 ratio. In pre-transplant patients and in those without GVHD this ratio resembled that in normal peripheral blood (1.44 +/- 0.5 and 2.46 +/- 1.3, respectively) but was significantly lower in both extraintestinal (0.71 +/- 0.08) and intestinal GVHD (0.56 +/- 0.08) (p less than 0.05). Acute intestinal GVHD was marked by a fourfold increase in CD57+ lymphoid cells within the epithelium and the lamina propria (p less than 0.05). The recognition of CD57+ cells, which may include natural killer-like cells, within rectal lymphoid infiltrates suggests a possible role for non-HLA restricted effector cells in GVHD of the rectum.
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PMID:Inflammatory cells in graft-versus-host disease on the rectum: immunopathologic analysis. 207 Jan 36


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