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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)

Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS.
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PMID:Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration. 175 80

Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD.
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PMID:Graft-versus-host disease in fully allogeneic small bowel transplantation in the rat. 291 75

The epidermolytic syndrome that can be obtained at will in F(1) hybrid hamsters by the cutaneous inoculation of adequate doses of parental strain lymphoid cells has been investigated to determine whether the cutaneous lesions are due to an autoimmune process arising from the severe, initial GVH reactions in the skin. It was amply demonstrated that inoculation of donor cells into the skin was of crucial importance to the development of epidermolysis. Parental strain lymphoid cells in similar doses delivered by any other route into normal F(1) hybrids failed absolutely to incite the acute syndrome. If "immune lymphocyte transfer" reactions incited by donor cells in the host's skin were surgically removed at timed intervals after inoculation, only complete excision within 24 hr prevented the appearance of epidermolysis in F(1) hybrid hosts, indicating that inoculated donor cells must remain within the confines of the skin for approximately 24 hr in order to evoke the disease, persistence for longer periods of time being unnecessary for the subsequent course of the disease. However, reconstitution experiments involving the intramuscular inoculation of suspensions containing mixtures of donor cells and host lymphoid cells, in the presence or absence of epidermal cells, unequivocally indicated that no intimate exposure of lymphoid cells to putative skin-specific antigens was essential. Similarly, the elicitation of generalized epidermolysis in F(1) hybrids irradiated with 300 r and then inoculated intravenously with donor cells casts further doubt on the pathogenic importance of the skin as a source of tissue-specific antigen. The results of subsequent experiments indicated that host leukocytes, rather than parenchymal cells of the dermis or the epidermis, were important contributors of the transplantation antigenic stimulus. Moreover, a series of experiments, using (CB x MHA)F(1) hybrid hosts that had been lethally irradiated and reconstituted with bone marrow cells from ALS-treated MHA donors, indicated that from 6 to 10 wk after reconstitution-when direct and immune lymphocyte transfer reactions showed a virtual absence of native F(1) leukocytes from the circulation-donor cells obtained from specifically sensitized MHA donors were completely ineffective in inducing epidermolysis, while equivalent lymphoid cell inocula derived from CB donors evoked the cutaneous disease irrespective of the time elapsed since reconstitution. To explain these findings it is postulated that in hamsters, the primary targets in graft-versus-host disease incited by the intracutaneous inoculation of donor cells are leukocytes originating in bone marrow or lymph node, or both.
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PMID:An analysis of graft-versus-host disease in Syrian hamsters. II. The epidermolytic syndrome: studies on its pathogenesis. 439 97

Sublethally (600 R) irradiated (CBA x C57BL)F(1) mice were grafted intravenously with parental lymph node cells in doses ranging from 0.2 x 10(6) to 12 x 10(6). The transplantation of these lymphoid cells leads to inactivation of the recipient's endogenous CFU (as measured by the diminution of the number of colonies registered on the 10th day after irradiation). A 50% inactivation was observed when the graft size of the CBA cells was 0.52 x 10(6). This figure for C57BL cells was 10 times more. This experimental system evaluates two simultaneously developing processes: the multiplication of endogenous CFU and the homograft reaction of transplanted lymphocytes against them. Both processes can be quantitatively estimated simultaneously in the same experiment by the determination of the number of colonies in corresponding experimental groups. Thus it was possible in a single experiment to compare quantitatively the effect of immunosuppressants on two points: (a) mitostatic action (suppression of CFU) and (b) lymphotoxic action. The latter, a true immunosuppressive effect, represents suppression of GVH activity of lymphoid cells and is demonstrated by abolition of the inhibition of endogenous colony formation. In the present system we have tested 6-MP, ALS, cyclophosphamide, hydrocortisone, and other drugs. The definite mitostatic and lymphotoxic doses of drugs are ascertained. Cyclophosphamide and ALS proved to be drugs with high dose ranges of selective lymphotoxic action. Hydrocortisone acetate had a more narrow range of selective lymphotoxic effect. 6-MP and Imuran (azathioprine) failed to exert any selective action on lymphoid elements. They possessed pronounced mitostatic efficiency, however.
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PMID:An experimental system for the simultaneous estimation of mitostatic and lymphotoxic effects of immunosuppressants and cytostatics. 439 41

Many different antilymphocytic antisera have been used clinically, and the properties of any particular type of ALS are not necessarily identical to those of any other type. Nevertheless, it is possible to draw certain general conclusions about the effects of ALS in human subjects. ALS administration has often been shown to reduce the number of circulating E-rosette-positive lymphocytes, although the precise mechanisms by which this reduction occurs are not known. Using a combined technique of E-rosette formation and immunofluorescence, heterologous immunoglobulin has been demonstrated on T and non-T lymphocytes from patients receiving non-selective ALS. Fifteen years' experience has failed to provide convincing support for the view that ALS (including immunoglobulin prepared from the whole antiserum) prolongs human renal allograft survival. It is not yet known whether ALS is a useful immunosuppressive agent in cardiac transplantation. One observation of possible clinical interest is that bone marrow regeneration has occurred in a number of patients with aplastic anemia who have been treated with ALS. No satisfactory method has been developed for monitoring the dose of ALS in human subjects. Appropriate studies may determine whether monoclonal antilymphocytic antibodies are clinically useful, for example in prolonging the survival of transplanted organs, in preventing or treating graft-versus-host disease, or in treating lymphoma, leukemia, or aplastic anemia.
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PMID:Clinical experience with antilymphocyte serum. 674 48

Transplantation tolerance was induced in A.TL mice to donors having disparity in the Ia antigens and identity at the H-2K, H-2D and non-H-2 antigens. After neonatal injection of 12 X 10(6) semiallogeneic lymphoid cells, permanent survival of A.TH skin allografts was observed in more than 90% of the recipients. Adoptive transfer of 50 X 10(6) lymphoid cells from normal A.TL donors to tolerant mice resulted in rejection of the tolerated grafts only in half of the animals. When cells from tolerant mice were tested in MLC and GVH assays, they reacted positively as did cells from normal mice. After sensitization in vitro, cells from tolerant mice were cytotoxic to A.TH antigens. Serum from tolerant mice did not inhibit cell proliferation in MLC assay nor blocked cytotoxic reaction in vitro and also did not enhance survival of A.TH skin grafts in normal A.TL mice. When the enhancing effect of this serum was tested in the recipients treated with ALS, prolonged survival of allografts was observed. Attempts to prolong survival of A.TH skin allografts by transfer of spleen cells from tolerant donors failed in normal A.TL recipients, while they were successful in the recipients treated with ALS. Long-term tolerated A.TH allografts, when transferred to normal A.TL recipients, were rejected. The findings show that loss of antigenicity of the tolerated skin allografts is not the mechanism of tolerance in this model and that cells capable of recognizing antigens of the tolerated allografts and reacting against them are still present in tolerant animals. Tolerance of skin allografts disparate only in Ia antigens, as has been shown at least for the strain combination tested, is probably mediated by the positive serum and cell suppressor mechanisms that block in vivo the effector phase of allotransplantation reaction.
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PMID:Mechanisms of tolerance of the Ia antigen disparate skin allografts. 676 Nov 52

We have shown that donor-specific unresponsiveness to cardiac and islet allografts can be induced by intrathymic (IT) inoculation of uv-B-irradiated spleen cells or resting T-cells in the Lewis-to-ACI rat combination. To examine if tolerance to cardiac and small intestinal allografts can be induced in adult animals, we employed intrathymic inoculation of resting donor T-cells combined with sublethal total body irradiation of 200 rads on Day -7 relative to organ transplant and consistently induced permanent donor-specific cardiac allograft survival (> 300 days) and small bowel transplant (SBT) survival (> 100 days) in the Lewis-to-ACI rat combination. Similarly, IT inoculation of T-cells on Day -7 combined with 1 ml ALS on Days -7 and 0 relative to SBT resulted in indefinite donor-specific graft survival (> 100 days) in all recipients without any evidence of graft-versus-host disease (GVHD) in the high responder of Wistar-Furth (WF)-to-Lewis rat combination. In contrast, WF SBT was promptly rejected in recipients pretreated with intravenous administration of donor T-cells and ALS, thus confirming the privileged position of the thymus in the induction of tolerance. The long-term unresponsive ACI recipients challenged 150 days after cardiac transplant with a second-set graft specifically and permanently (> 120 days) accepted the second-set SBT without rejecting the primary cardiac grafts and without developing GVHD. Third-party grafts were rejected in a normal fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of donor-specific tolerance to rat cardiac and small bowel allografts by intrathymic inoculation of donor T-cells. 833 31