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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)

Growth of transplantable KMT-17 tumour in syngeneic WKA/MK rats was inhibited by i.v. preimmunization with whole blood from normal rats of allogeneic strains. The inhibitory effect was also observed in rats immunized with allogeneic white blood cells alone. The strength of the inhibitory effect mainly depended on the the strain of donor rat used; blood from Donryu and Kyoto strain rats produced the strongest inhibition, blood from Tokyo and Fischer strain rats produced moderate inhibition to the syngeneic tumour growth. Blood from ACI/N strain rats did not produce the inhibition. The mechanism of blood transfusion in inhibiting tumour growth is not yet clear. However, it seems that GVH reaction does not play an important role in the mechanism of the inhibition effect, because the effect was obtained by immunization with mitomycin C-treated allogeneic white blood cells and also by the immunization effect may be due to nonspecific active immunization. Significance of blood transfusion with special reference to clinical immunogtherapy of cancer is discussed.
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PMID:Anti-tumour immunity by normal allogeneic blood transfusion in rat. 1 11

Graft failure in recipients of lymphocyte-depleted allogeneic bone marrow transplants is a major limitation to the success of this approach for preventing acute graft-versus-host disease. In a rat BMT model, we evaluated the effect of cyclosporine dose and schedule of administration on the engraftment of MHC-mismatched bone marrow. Lewis Brown-Norway rat recipients were prepared with myeloablative doses of busulfan (day -2) and cyclophosphamide (day -1) and then transplanted with MHC-mismatched ACI rat BM (day 0) that had been depleted of lymphocytes by counterflow centrifugal elutriation. Beginning on day -1, LBN rats received variable doses of CsA (i.e., 12.5, 10.0, 7.5, 5.0, 2.5, 0.0 mg/kg/day) for various lengths of time after BMT (i.e., 7, 14, 21, or 28 days). While all rats receiving high-dose CsA (i.e., 12.5 or 10.0 mg/kg/day) for 28 days had stable donor-derived hematopoietic reconstitution, rats receiving a daily dose of CsA less than or equal to 5.0 mg/kg/day or CsA for less than or equal to 21 days had a high incidence of graft failure. The data argue that (1) graft resistance can be suppressed by CsA and (2) the effectiveness of CsA for securing engraftment is dependent upon both dose and duration of treatment.
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PMID:Prevention of graft failure by cyclosporine in rats receiving lymphocyte-depleted MHC-mismatched bone marrow. 154 56

Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model. Transplants between strongly histoincompatible ACI and Lewis (LEW) strain rats, and their F1 progeny are performed so that graft rejection alone is genetically permitted (F1----LEW) or GVHD alone permitted (LEW----F1) or that both immunologic processes are allowed to occur simultaneously (ACI----LEW). Specific doses of FK-506 result in prolonged graft and host survival in all genetic combinations tested. Furthermore, graft rejection is prevented (ACI----LEW model) or inhibited (rejection only model) and lethal acute GVHD is eliminated. Even at very high doses, cyclosporine did not prevent graft rejection or lethal GVHD, nor did it allow long-term survival of the intestinal graft or the host. Animals receiving low doses of cyclosporine have outcomes similar to the untreated control groups. No toxicity specific to FK-506 is noted, but earlier studies by other investigators suggest otherwise.
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PMID:The use of FK-506 for small intestine allotransplantation. Inhibition of acute rejection and prevention of fatal graft-versus-host disease. 169 Apr 69

Severe graft-versus-host disease was induced by transplantation of ACI rat bone marrow and spleen cells into irradiated Lewis rat recipients. Treatment with FK 506 or cyclosporine A (CsA) was started after clinical and histologic evidence of acute GVHD was present. A 14-day course of FK 506 at 1.0 mg/kg/day could rescue 100% of the animals suffering from GVHD. In contrast only one half of the animals treated with CsA at a high dose of 25 mg/kg/day recovered. After cessation of immunosuppressive therapy, FK 506-treated animals displayed a marked prolonged disease-free interval as compared to CsA-treated bone marrow recipients. Recurrence of the disease in these animals could be prevented when FK 506 treatment was continued after the induction period with a low maintenance dose of 0.1 mg/kg/day every other day.
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PMID:FK 506 reverses acute graft-versus-host disease after allogeneic bone marrow transplantation in rats. 171 58

A rat model of combined pancreas-spleen transplantation (PST) was used in order to characterize the immunologic consequences of PST when compared to pancreas transplantation (PT) alone. Weakly MHC disparate Fischer (F344) PST grafts survived significantly longer in LEW recipients than did F344 PT grafts (17.6 +/- 3.4 vs 12.1 +/- 1.0 days, respectively, P less than 0.001). However, graft versus host disease (GVHD) occurred regularly in the PST recipients. Similarly, in haploidentical LBN to LEW donor-recipient pairs, PST graft survival was also modestly but significantly increased over that of the PT controls (10.6 +/- 1.0 vs 8.5 +/- 0.8 days, respectively, P less than 0.001). Conversely, in the ACI to LEW combination where MCH differences are very strong, PST graft survival was not longer than PT controls (7.5 +/- 0.8 vs 7.0 +/- 0.6 days, respectively, P greater than 0.2). GVHD was not observed in either of the latter two experiments. Short-term immunosuppression with cyclosporine further improved the outcome in LEW recipients of F344 grafts by inducing long-term graft survivals in approximately one-fourth of the PST recipients. Host splenectomy did not improve graft survival in PST recipients but did increase the risk of GVHD in LEW recipients of F344 PST grafts. Graft irradiation prior to transplantation with 500 rad not only abrogated the GVHD potential of the F344 PST graft but also eliminated the graft survival prolonging effect of the donor spleen. Donor spleen cells injected at the time of PT in F344 to LEW transplants resulted in graft prolongation not different from spleen intact PST recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic consequences of combined pancreas-spleen transplantation in the rat. 266 20

The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan-T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts.
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PMID:Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads. 266 98

We have investigated the immunosuppressive effects of thalidomide (Thal) in a bone marrow transplant (BMT) model for graft-versus-host disease (GVHD). Lewis rats received RT1-incompatible marrow transplants from ACI rats after total-body irradiation. Twenty-two of twenty-three rats with established severe acute GVHD were successfully treated with Thal. Thal was given for therapy by gavage at 50 mg/kg/day or 100 mg/kg/day for 40 days after GVHD was clinically and histologically present. Fourteen of twenty-two received prophylaxis successfully with Thal at a dose of 50 mg/kg/day or 100 mg/kg/day. Acute GVHD did not develop after the drug was stopped. Three animals treated for severe GVHD later developed chronic GVHD. Chimerism was shown by permanent acceptance of ACI skin grafts and rejection of third-party skin grafts. Lymphocytes from Thal-treated animals likewise did not respond to Lewis or ACI cells in mixed lymphocyte culture but responded to third-party BN lymphocytes. Thal appears to be a potent new agent for therapy and prophylaxis of GVHD.
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PMID:Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model. 293 10

We have developed a simple three flow-rate, fixed rotor speed, counterflow centrifugal elutriation (CCE) procedure that permits the isolation of an engraftable lymphocyte-depleted (greater than 98%) fraction from ACI rat bone marrow. The different cell fractions were characterized by morphology, alloreactivity in mixed lymphocyte culture and limiting dilution analysis, colony-forming capacity, and their capacity to reconstitute hematopoiesis and effect a graft-versus-host reaction in lethally irradiated allogeneic hosts. After CCE fractionation of ACI rat marrow, transplantation of the lymphocyte-depleted marrow fraction resulted in sustained engraftment without evidence of clinical or histologic acute graft-versus-host disease (GVHD). CCE fractionation of rat bone marrow may be a useful preclinical model for studying lympho-hematopoietic and immune reconstitution after transplantation with lymphocyte-depleted donor marrow, as well as for studying the role of lymphocyte subpopulations on engraftment, acute GVHD, and leukemia relapse in syngeneic and allogeneic bone marrow transplantation.
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PMID:Separation of rat bone marrow cells by counterflow centrifugal elutriation: a model for studying the effects of lymphocyte depletion. 325 46

LEW recipients of ACI vascularized hind limb allografts were analyzed for lymphoid chimerism by a complement-dependent cytotoxicity assay using antisera produced across this strain combination. In assessing the technique, two LEW recipients of sublethal irradiation (400 rad), ACI bone-marrow allografts, and CsA exhibited mixed lymphoid chimerism 23 days posttransplant. Short-term CsA-treated CTA recipients that were assayed at various times following transplantation and underwent subacute rejection did not demonstrate any significant mixed lymphoid chimerism. Long-term CsA-treated CTA recipients that were assayed at various times prior to 100 days posttransplant also did not demonstrate any significant mixed lymphoid chimerism. However, following extensive CTA survival (greater than 100 days) significant mixed donor-host lymphocyte chimerism became evident in the peripheral blood, and in one recipient a large quantity of donor bone marrow remained viable in the ACI limb allograft at necropsy (greater than 200 days posttransplant). The development of donor-host lymphocyte chimerism and a wasting syndrome that followed long-term CTA survival was suggestive of GVHD.
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PMID:Lymphocyte chimerism in a full allogeneic composite tissue (rat-limb) allograft model prolonged with cyclosporine. 325 42

Intestinal inflammation occurs in both nematode infections and graft-versus-host disease (GVHD). In nematode infections, this involves the proliferation of mucosal mast cells (MMC) and goblet cells (GC). To examine MMC and GC responses in GVHD, female Lewis rats were given allogeneic bone marrow (BM). Each animal received 1,020 rads and, one day later, 6 X 10(7) ACI BM cells plus 2 X 10(7) ACI spleen cells i.v. Control rats received 6 X 10(7) BM cells. On days 4, 8, 12, 16 and 20 post-transplant, rats were sacrificed and their intestines removed and prepared for histological examination of MMC and GC. Cells in 10 villus-crypt units (VCU) of the gut were counted for each animal. Skin and tongue were also removed and examined to determine the degree of GVHD. GVHD was first evident on day 8 in allogeneic BM recipients and progressed thereafter. No evidence of GVHD was seen in syngeneic BM recipients. Rats receiving allogeneic BM showed a 10-fold increase from day 12 to day 20 (p less than 0.01). Rats receiving syngeneic BM showed no significant change in MMC through the 20th day. In animals with GVHD, GC decreased by day 12 and remained lower than control animals during the subsequent 8 days. It was concluded that, similar to nematode infection, MMC proliferation is a feature of GVHD. In contrast, GC do not appear to proliferate in an acute GVHD.
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PMID:Gut mucosal mast cells and goblet cells during acute graft-versus-host disease in rats. 354 68


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