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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)

Spleens from Lewis X BN F1 hybrid rats were directly anastamosed to the circulation of parental strain Lewis rats by a microvascular technique; no immunosuppressive drugs were given. Donor spleens enlarged massively during the first month after implantation, then grew gradually smaller over succeeding months without compromising their blood supply. Renal allografts were placed into bilaterally nephrectomised recipients that had already borne a splenic allograft for three months. The grafts functioned perfectly and showed no signs of rejection five months later. Donor LBN skin allografts transplanted to these animals showed markedly prolonged survival while third-party BUF rat skin allografts were rejected in first-set fashion. High titres of anti-LBN haemagglutinating antibody could be detected in the circulation of spleen-grafted animals during the first month; the titres fell to zero by the fourth month. Cellular reactivity of recipient cells against LBN antigens measured by the popliteal node GVH assay fell to minimal levels by the third month. These data indicate that the immune response to allografted tissues may be specifically and markedly suppressed in adult animals by continued presence of a donor-strain spleen.
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PMID:Induction of secific immunological tolerance to histocompatible renal and skin allografts after donor strain spleen implantation. 77 33

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

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

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.
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PMID:Graft-versus-host disease associated with intestinal transplantation in the rat. Host immune function and general histology. 279 6

A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence.
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PMID:Graft irradiation abrogates graft-versus-host disease in combined pancreas-spleen transplantation. 351 91

The histopathological changes and the course of graft-versus-host (GVH) disease were studied in the rat model of small-bowel transplantation using the Lewis----LBN-F1 strain combination. Allograft-induced GVH disease led to the recipients' death from enteritis, dermatitis and emaciation after 14.4 +/- 2.9 days (heterotopic grafts) and 14.0 +/- 0.7 days (orthotopic grafts). Histologic evidence of dermatitis (epidermal hyperkeratosis and cutaneous infiltration by mononuclear and polymorphonuclear cells) and enteritis (villous blunting and sloughing, inflammatory infiltrate of the recipient's own intestine) appeared on the 9th to 13th postoperative days, and these changes became fulminant within 2-3 days. The lymphatic tissues of the Lewis grafts and the LBN-F1 host underwent a course of progressive lymphoid depletion and loss of follicular architecture beginning on the 5th postoperative day. Throughout the postoperative course, the small-bowel graft remained intact. The relative spleen weight progressively increased until shortly before death, when a marked reduction was observed. The clinical triad of diarrhea, diffuse dermatitis, and hypertrophy of the lymphoid organs followed by their atrophy suggests a diagnosis of GVH disease rather than rejection of the small-bowel allograft. The diagnosis can be confirmed by biopsy of a recipient lymph node or the intestinal allograft (cave perforation) if it is accessible.
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PMID:Graft-versus-host disease induced by small bowel allografts. Clinical course and pathology. 395

The development of either unstable immune chimerism and lethal graft-versus-host disease or stable immune chimerism and alloimmune tolerance can result from extremity transplantation. LBN rats served as recipients of Lewis vascularized extremity (limb) transplants. Recipients received no immune suppression and were immunologically unmodified. The bone marrow of transplanted and contralateral limbs was analyzed in situ for distribution of nuclei, nuclear area, and staining intensity by digital image analysis and computerized morphometry. Cellularity was significantly increased, and fat content was significantly decreased in the graft-versus-host disease animals' marrow versus the tolerant animals' marrow for both the transplanted and contralateral limbs. Tolerant animals demonstrated significantly increased nuclear staining compared with graft-versus-host disease animals for both transplanted and contralateral limbs. Additionally, there were significant changes between the host and the transplanted limbs for marrow intensity and cellularity within tolerant and graft-versus-host disease groups. The significant differences in the graft-versus-host disease-positive recipients suggested that both autoimmune dysregulation and alloimmune reactions were in effect for both donor and host bone marrow compartments. Cellular alterations in the tolerant recipients' marrow were suggestive of subtle subclinical graft-versus-host responses.
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PMID:Graft-versus-host disease in extremity transplantation: digital image analysis of bone marrow in situ. 757 77

Endothelin (ET-1) expression was evaluated by radioimmunoassay in both plasma and various tissue specimens serially obtained from LBN-F1 recipients of LEW heterotopic small bowel allografts. The recipients showed graft-versus-host disease (GVHD), which histologically became apparent on postoperative day (POD) 13. The ET-1 levels peaked on POD 9 in the kidney, lung, and host intestine at 51.0 +/- 21.1, 90.9 +/- 59.6, and 25.4 +/- 11.8 pg/g wet, respectively, and peaked on POD 11 in the plasma at 7.7 +/- 3.2 pg/ml; thereafter, they decreased to basal levels in both the plasma and tissue specimens on POD 13. An immunohistochemical study of these organs showed a corresponding increase in ET-1 staining in both the endothelial and epithelial cells on PODs 5 and 9, and a reduction in staining on POD 13. In conclusion, ET-1 was found to be increasingly released from the target cells of GVHD before any histological changes became apparent, thus suggesting the pathophysiological involvement of ET-1 in intestinal GVHD.
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PMID:Involvement of endothelin in graft-versus-host disease after rat small bowel transplantation. 908 97

The use of inbred mouse strains of defined genetic background has allowed for the development of systems capable of reproducibly generating either an acute or chronic graft-versus-host disease (GvHD). The malononitrilamides MNA 279 and MNA 715, analogues of the main metabolite of leflunomide, have been shown to directly inhibit T-cell proliferation and B-cell functions. Therefore, they have been studied in a local GvH reaction in the popliteal lymph node (PLN) assay in LBN rats, on the development of an acute and lethal GvHD in B6C3F1 mice and on a chronic autoimmune GvHD in BDF1 hybrid mice. In the PLN assay an oral administration of various concentrations (7.5 to 50 mg/kg) of both MNAs inhibited the localized GvH reaction dose-dependently and suppressed the lymph node hyperplasia. Both MNAs also acted therapeutically in this assay when they were given as late as day 4 or 5 after challenge. In the model of an acute lethal GvHD the treatment of the GvH-B6C3F1 hybrid mice with the MNAs (2.5 to 20 mg/kg/day) shortly after disease induction on days 3 to 12 resulted in a dose-dependently improved survival rate. With 20 mg/kg of drugs, mortality of this life-threatening GvHD was completely prevented and also other parameters like splenomegaly, erythrocyte counts and hematocrit values were strongly suppressed. Treatment of sensitized GvH-BDF1 hybrid mice in the chronic autoimmune-like model with the MNAs (30 mg/kg/day), given on days 3 to 36 by oral gavage, resulted in an improved survival rate, inhibited lymphadenopathy and splenomegaly, reduced the levels of autoantibodies and other immunoglobulins like IgE and IgG1, prevented proteinuria and the development of glomerulonephritis. Both MNA 279 and MNA 715 can inhibit ongoing aberrant immune responses in animals suffering from GvHD.
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PMID:The new immunosuppressants, the malononitrilamides MNA 279 and MNA 715, inhibit various graft-vs.-host diseases (GvHD) in rodents. 951 26

This laboratory has used a composite tissue allograft model as a vehicle for studies on a new type of bone marrow transplant, the vascularized bone marrow transplant. The model consists of a rat hind limb transplant that incorporates integumentary musculoskeletal, and lymphopoietic tissues. These transplants, in comparison with conventional marrow transplants, have the advantage of providing a syngeneic microenvironment and immediate engraftment of both mature and progenitor hemopoietic cells at the time of transplantation. The characteristics of graft-versus-host disease were studied in this model. Lewis X Brown Norway F1 (LBN RT-1(1+n)) rats received hind limbs from Lewis (LEW RT-1(1)) donors (n = 19). Animals were observed daily for signs of graft-versus-host disease. Necropsies were performed. A minority of animals developed lethal disease (7 of 19 recipients) and demonstrated cachexia with concomitant histopathologic changes of the disease. Acute and chronic groups emerged with distinct clinical courses, which are similar to other models of this disease. Recipients of vascularized bone marrow transplants (limb transplants) showed clinical and histopathologic changes of the disease. The transplants may be used as a model of graft-versus-host disease in humans. Most interestingly, the transplant has a lower incidence of disease compared with other methods of bone marrow transplantation and represents an alternative to conventional bone marrow transplantation, which deserves further exploration. It may be possible to develop a new technique for bone marrow transplantation based on this surgical approach. It is proposed that the transfer of vascularized blocks of bone/marrow into prospective recipients as opposed to cellular bone marrow transplants may be preferable.
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PMID:Composite tissue allografts in rats: IV. Graft-versus-host disease in recipients of vascularized bone marrow transplants. 1051 19


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