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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)

The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras.
Cell Immunol 1986 Sep
PMID:Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow. 294 11

Counterflow centrifugation elutriation (CCE) has been used to separate moderate quantities of bone marrow (BM) into distinct cell populations for further in vitro investigation. Recently, this technique was employed to reduce the incidence of graft-versus-host disease (GVHD) in human allogeneic bone marrow transplantation (BMT) by removing the majority of mature lymphocytes from the graft. Unfortunately, current methods employing the small (J6-B) elutriator rotor require time consuming preseparation steps and multiple runs. We report our experience with a fixed rotor speed, two-flow rate elutriation procedure using the new Beckman JE-10X rotor system which can separate more than 10(10) nucleated BM cells in 30 min. Three fractions were obtained which differed in size, morphology, and immunologic capacity. The large cell fraction is suitable for allogeneic BMT since it is radically depleted of mature T lymphocytes and retains high clonogeneic capacity.
J Immunol Methods 1986 Sep 27
PMID:Large scale separation of human bone marrow by counterflow centrifugation elutriation. 294 69

Cryptosporidiosis may cause diarrhea after a conditioning regimen for allogeneic bone marrow transplantation. The case reported here suggests resurgence of latent cryptosporidiosis in early post-graft period, since other causes of immunosuppression such as graft-versus-host disease or transfusional LAV/HTLV III retroviral infection, were absent. The diagnosis was confirmed by rectal biopsy and ultrastructural analysis. Good response to spiramycin was obtained.
Presse Med 1986 Sep 20
PMID:[Cryptosporidiosis in grafting of allogeneic bone marrow]. 294 61

The inoculation of B6D2F1 mice with T lymphocytes from the C57BL/6 parental strain induces an "immunosuppressive" graft-vs-host reaction (B6 GVH), whereas inoculation of T cells from the other, DBA/2 parental strain induces an "immunostimulatory" GVH reaction and a lupus-like disease (DBA GVH). The present study compares cytotoxic T lymphocyte (CTL) function in the spleens of these GVH mice as well as differences in the donor inoculum that could account for these different types of GVH. We observed that the B6 GVH induces an immunodeficiency that encompasses CTL precursors (and possibly T helper cells) and results in suppressor cells that abrogate responses to both trinitrophenyl (TNP)-modified self and third party alloantigens. In contrast, the DBA GVH induces only a T helper cell immunodeficiency and results in suppressor cells selective for class II restricted L3T4+ T helper cells. Chimeric T cells were detected in both types of GVH. In the B6 GVH both L3T4+ and Lyt-2+ donor cells were observed, although Lyt-2+ cells predominated. In the DBA GVH, donor T cells were almost exclusively of the L3T4+ phenotype. The lack of appreciable donor Lyt-2+ cells in the DBA GVH can be explained by a defect in the DBA donor inoculum manifested by a naturally occurring two-fold reduction in Lyt-2+ cell numbers as well as a nine-fold reduction in CTL precursors with anti-F1 specificity. T cells in the DBA inoculum, therefore, are predominantly L3T4+. A similar defect induced in B6 donor cells by anti-Lyt2 antibody and complement not only converted the suppressive GVH to a stimulatory GVH, as measured by anti-DNA antibodies, but also resulted in a T cell immune deficiency characteristic of the DBA GVH, i.e., a selective loss of the TNP-self CTL response. Thus the presence or absence of adequate numbers of functioning Lyt-2+ cells in the donor inoculum is correlated with the development of either a suppressive or stimulatory GVH, respectively. That donor Lyt-2+ cells mediate a suppressive GVH through cytolytic mechanisms is evidenced by greater than 70% reduction in B6 GVH spleen cell numbers and readily demonstrable anti-F1 CTL activity by these spleen cells despite an inability to generate anti-allogeneic or anti-TNP self CTL activity even in the presence of added T helper factors.(ABSTRACT TRUNCATED AT 400 WORDS)
J Immunol 1987 Sep 15
PMID:Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease. 295 40

Dual labeling with the monoclonal antibodies anti-Leu 2 (fluorescein-conjugated) and anti-Leu 15 (phycoerythrin-conjugated) was used to phenotype and sort the lymphocytes from 12 short-term (100 days postgrafting) recipients, 8 long-term (6 months postgrafting) stable, and 11 long-term patients with chronic graft-versus-host disease (GVHD). The proportion of Leu 2+ 15+ cells was increased in 11 of 12 short-term patients (mean + SEM: 31% +/- 3.6)-and in 6 of 11 patients with chronic GVHD (18% +/- 2.4) compared with normal controls (n = 8; 7.5% +/- 1.9). However, there was no correlation between proportions of Leu 2+ 15+ or Leu 2+ 15- cells and the presence of acute GVHD. Long-term patients with chronic GVHD tended to have a higher proportion of Leu 2+ 15- cells. To functionally characterize these two T cell subsets, Leu 2+ 15- and Leu 2+ 15+ subsets were sorted from purified T cells obtained from two recipients and one normal subject. Both Leu 2+ 15+ and Leu 2+ 15- cells from a short-term patient suppressed pokeweed mitogen--stimulated immunoglobulin production of normal B cells. Leu 2+ 15- cells from a long-term survivor with chronic GVHD and the normal control provided help, whereas the Leu 2+ 15+ cells also strongly suppressed immunoglobulin synthesis. The suppressor activity of the Leu 2+ 15+ subset in all three individuals was radiosensitive (12 Gy). These results illustrate the need for careful correlative phenotyping and functional studies. Furthermore, these studies clearly demonstrate that different functions may exist within a particular T cell phenotype after bone marrow transplantation.
Transplantation 1987 Sep
PMID:Phenotypical and functional studies on a subtype of suppressor cells (CD8+/CD11+) in patients after bone marrow transplantation. 295 35

Graft versus host disease is associated with a myriad of cutaneous signs and few nail manifestations. A case of documented chronic graft versus host disease with the initial cutaneous presentation of white superficial onychomycosis is presented. The patient developed a lichenoid eruption in an unusual distribution and a reticulated hyperpigmentation of the face. Culture of the nails was positive for Trichophyton rubrum, an uncommon cause of white superficial onychomycosis, this being the third known reported case. Histopathologic examination revealed fungal elements in the superficial nail plate with an absence of fungus in the ventral aspect of the nail plate. A summary of cutaneous skin and nail manifestations in graft versus host disease is presented.
Cutis 1987 Sep
PMID:Onychomycosis in graft versus host disease. 295 42

Data from human clinical trials and animal experiments have suggested that T lymphocytes in donor marrow help to facilitate engraftment after allogeneic bone marrow transplantation, possibly through a suppressive effect on the immunity of the recipient. In previous studies marrows from HLA-identical donors were treated ex vivo with a mixture of eight monoclonal antibodies together with rabbit complement to achieve a 3-log depletion of T cells and CD3-negative lymphoid cells. Transplantation of this marrow was associated with a 27% actuarial risk of graft failure in leukemic recipients conditioned with cyclophosphamide (120 mg/kg) and 15.75 Gy fractionated total body irradiation. In the present study, we employed an anti-CD3 ricin A-chain-containing immunotoxin (64.1-A) together with 20 mM NH4Cl to achieve a selective 3-log depletion of CD3-positive cells. The patient entry criteria and pretransplant conditioning regimen were identical to those used in previous studies. Despite the differences in marrow treatment, the clinical outcome of the present study was similar to that obtained previously. Graft-versus-host disease (GVHD) was largely prevented without the need for post-transplant immunosuppression, but two of the eight patients developed graft failure. These results indicate that CD3-negative cells have little or no ability to initiate GVHD. To the extent that graft failure in this study was not caused by stem cell damage or loss of CD3-negative cells during ex vivo processing of the marrow, it appears that the lymphoid cells required for facilitating allogeneic engraftment under these conditions are CD3-positive.
Bone Marrow Transplant 1988 Sep
PMID:Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. 297 60

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.
Blut 1988 Sep
PMID:Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation. 304 89

Graft-versus-host disease (GvHD) prophylaxis using methotrexate (23 patients) and T-cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T-cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD-associated mortality from 79% to 5%. Actuarial disease-free survival for low-risk patients (57% with T-cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T-cell depletion. Prevention of graft failure after T cell-depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.
Eur J Haematol 1988 Sep
PMID:T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia. 305 41

Two opposing immunologically-mediated phenomena currently limit the success of bone marrow transplantation (BMT) in HLA-identical situations and impede the application of this therapeutic modality across MHC barriers. These phenomena are: (1) the response of T cells within the donor marrow allograft to recipient alloantigen, resulting in graft-versus-host disease (GVHD) with its attendant morbidity and mortality; and (2) the response of recipient cells which have survived the ablative conditioning regimen against alloantigen borne by the donor marrow allograft, leading to failure of alloengraftment. While T cell depletion of donor marrow has successfully reduced the incidence of severe GVHD, this reduction has been associated with an increased incidence of failure of alloengraftment. In this communication we review several recent approaches being studied in animal models in our laboratory to avoid such undesirable effects of host-anti-donor and donor-anti-host alloaggression. The first approach is based on the observation that administration of T cell-depleted (TCD) syngeneic bone marrow (BM) appears to limit GVHD while still permitting engraftment by co-administered non-TCD allogeneic BM. This anti-GVH effect of TCD syngeneic marrow can be enhanced by delaying the administration of allogeneic BM by 8 days following whole body irradiation and syngeneic BMT. Evidence that natural suppressor cells derived from syngeneic marrow may be responsible for this phenomenon is reviewed. We also present evidence for the existence of a non-stem cell bone marrow subpopulation, distinct from those T cells which cause GVHD, which is capable of increasing levels of allogeneic chimerism.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Marrow Transplant 1988 Sep
PMID:Achieving alloengraftment without graft-versus-host disease: approaches using mixed allogeneic bone marrow transplantation. 305 45


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