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)

We studied the effect of Cyclosporin A on the thymus in rats. A daily subcutaneous injection of Cyclosporin A at a dose of 45 mg/kg body weight in young adult rats resulted in a 100% mortality within two weeks. Daily administration of 15 mg/kg for two weeks was well tolerated. Rats treated at this dose showed whole blood Cyclosporin concentrations around 6 mg/l. The thymus immediately after treatment showed the almost complete disappearance of the medulla, including the microenvironment made by medulla-type epithelium, interdigitating dendritic cells defined by their expression of MHC class II antigen, and lymphocytes with a mature T-cell phenotype. After discontinuation of Cyclosporin treatment, a rapid recovery occurred, with the reappearance of medulla areas after 2 weeks. These areas differed from the normal medulla by the absence of medulla-type epithelium. This cell population recovered in its normal location in about 4 weeks. The reappearance of medullary interdigitating cells was associated with reappearance of lymphocytes with a mature T-cell phenotype. In the regenerating thymus "holes" in the microenvironment were observed that lacked epithelium and interdigitating cells, and that were filled by lymphocytes with an immature cortex phenotype. Peripheral lymphoid organs, of which the spleen was studied in more detail, did not manifest changes in lymphoid and stromal components. Target organs for syngeneic graft-versus-host disease, as described under special conditions after Cyclosporin treatment, did not show any histologic abnormality. The changes in thymus (immuno)histology may be associated with changes in shaping the T-cell repertoire: but, clinical manifestations of such changes require special experimental conditions.
Thymus
PMID:Cyclosporin and the rat thymus. An immunohistochemical study. 229 25

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated for 40 or 80 days with Cyclosporin A (Cy-A) contract disease mimicking graft-versus-host disease about 3 weeks after withdrawal of the drug. We investigated the reconstitution of peripheral blood lymphocytes after this treatment. A selective effect on the regeneration of the CD4+ cells was observed. During Cy-A administration CD4(+)-cell regeneration was almost completely suppressed, but within 3 weeks after withdrawal of the drug such cells reappeared in blood and reached pre-irradiation levels about 6 weeks later. The coincidence of the reappearance of CD4+ cells and the onset of autoimmune disease suggests a causal relation between both events.
Thymus 1989
PMID:Perturbation of T-cell differentiation in lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporin-A. 251 75

Fetal liver transplants (FLT) were carried out in 25 beagles under various conditions. Graft recipients were prepared with fractionated total body x-irradiation (TBI) of 3 X 6 Gy or 2 X 6 Gy and rescued with cryopreserved fetal liver cells (FLC) from 51- to 52-day-old or 43- to 46-day-old, DLA-identical siblings or DLA-haploidentical, homozygous half-siblings. In all groups, FLC grafts contained comparable numbers of granulocyte-macrophage progenitor cells. Initial engraftment was achieved in all dogs. However, low TBI dose and DLA haplotype disparity between donor and recipient were associated with graft failure in 1/3 and 2/9 recipients, respectively, within 10-16 days of treatment. Lectin-responsive host type lymphocytes circulated for more than 5 weeks, whereas bone marrow metaphases were always of donor sex. Reduced TBI dose and young donor age were associated with delayed granulocyte recovery. Moreover, circulating platelets and total lymphocytes as well as T and B-cell numbers and rose more slowly in recipients of immature FLC grafts than in the other groups. Delayed cutaneous hypersensitivity reactions were normal one year after FLT, whereas the IgM component of the hemagglutinin response to sheep red blood cells was depressed. In mixed leukocyte culture, chimeric lymphocytes were tolerant to host antigens. Nonetheless, clinical and histological signs compatible with low-grade graft-versus-host disease were recorded in 10 or 25 animals. Thus FLT in dogs could be carried out, even across DLA barriers, without severe graft-versus-host disease. However, a low pretransplant TBI dose, incomplete DLA match and young age of the fetal donor were associated with graft rejection and protracted restoration of hemopoiesis and immune functions.
Thymus 1987
PMID:Variation of treatment conditions alters the outcome of fetal liver transplantation in dogs. 296 15

Theophylline (Th) augments suppressor T cell activity (STCA). We attempted to test this immunoregulatory effect of TH on survival, renal disease and several immunologic parameters in NZB/W F-1 female mice. The median survival was 274 +/- 50 days for the mice receiving Th and 235 +/- 39 days for the controls (p less than 0.01). Assessment of the extent of renal damage by light microscopy revealed activity scores of 1.86 +/- 2 and 4.71 +/- 2.7 for the Th and control groups, respectively (p less than 0.001). T cell activity of NZB/W F-1 lymphocytes was assessed by the local xenogeneic GVH reaction. The mean GVH reaction volume of the Th group was significantly lower (9.3 +/- 8.8 mm3) as compared to controls (31 +/- 9 mm3) (p less than 0.001). The proportion of Lyt-1 versus Lyt-2 spleen lymphocytes did not change significantly. It is concluded that Th prolongs survival and decreases the extent of renal damage in female NZB/W F-1 mice.
Thymus 1988
PMID:Theophylline prolongs survival and decreases renal damage in female NZB/W F-1 mice. 297 91

Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery, or altering long-term survival.
 ...
PMID:Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 to 12 years' follow-up. 305 51

MRL/l mice, which are homozygous at the lpr locus, can be inhibited in lpr phenotype expression (lymphadenopathy, accelerated death) by a transfer of MRL/n bone marrow cells following X-irradiation of the recipients (MRL/n bone marrow----X-irradiated MRL/l chimeras). Female MRL/l bone marrow----X-irradiated MRL/l chimeras express the lpr phenotype with a delay corresponding to the age at the time of cell transfer. However, the equivalent male chimeras resemble MRL/n bone marrow----X-irradiated MRL/l chimeras. When the reverse MRL/l bone marrow----X-irradiated MRL/n chimeras are constructed, one finds that whichever the sex is, the chimeras undergo a wasting disease looking like a graft-versus-host disease, with particularly a marked atrophy of the spleen. A similar GVH like disease is observed with C57Bl/6 lpr bone marrow----X-irradiated C57Bl/6 normal mice. These animals survive at least 5 months but manifest a spleen aplasia. When reconstituted with MRL/n bone marrow, MRL/l recipients develop higher levels of antinuclear and anti-ds/ss DNA antibodies than MRL/n recipients. This suggests that the 'lpr environment' of the host may have an influence on the development of B cell hyperactivity.
Thymus 1987
PMID:Bone marrow transfers in X-irradiated mice congenic at the lpr locus: some paradoxical effects. 331 28

We studied the ability of fetal liver cells to reconstitute hematopoiesis and immunity in lethally irradiated dogs. Engraftment and sustained lymphoid and hematopoietic recovery was achieved when the recipients received a preparative regime of high-dose total body irradiation (TBI) alone followed by transplantation of DLA-identical fetal liver. The combination of high-dose TBI and cyclosporine allowed engraftment in DLA-mismatched fetal liver transplants. Typical features of graft-versus-host disease (GvHD) did not occur although autoimmune-like syndromes (myasthenia gravis, immune thrombocytopenia) were observed in some recipients. Hematopoietic recovery was rapid and complete. Recovery of T- and B-lymphocyte function was comparatively delayed, but sufficient to prevent opportunistic infections after the initial 3 months post transplant. These data indicate that cells from a single fetal liver can reconstitute hematopoiesis and immunity in DLA-mismatched recipients and suggest that human fetal liver cell transplantation may be an effective source of stem cells for patients who lack an HLA-identical donor for bone marrow transplantation.
Thymus 1987
PMID:Sustained recovery of hematopoiesis and immunity following transplantation of fetal liver cells in dogs. 332 1

Fetal liver infusion (FLI) was tried as an alternate mode of therapy in 40 patients with aplastic anaemia and in 16 patients with acute myeloid leukaemia. The fetal HLA typing carried out on spleen and thymus cells revealed that, while it was more difficult to HLA type the thymus than the spleen cells, 'full house' antigens could be determined only in fetuses of 18 weeks or older. No special effort was made to transfuse HLA- matched or partially matched donor cells into the recipient. The recipients were HLA typed at varying time intervals following FLI in an attempt to document a possible chimerism. None of the patients revealed a 'shift' in their HLA antigen profile and there was no evidence of any donor cell engraftment. No relationship between the HLA match of donor and recipient, and the general condition, the prognosis or the total survival of the patient was evidenced. These data indicate that, even though fetal liver cells express HLA antigens, these cells are functionally incompetent to cause an apparent graft-versus-host disease in the host.
Thymus 1987
PMID:HLA status following fetal liver transplantation in aplastic anaemia and acute myeloid leukaemia. 332 2

This study reviews results of fetal liver transplantation in hematologic disorders including aplastic anemia, leukemia and thalassemia. One hundred and twenty two patients received transplants for aplastic anemia; engraftment was reported in 4 patients; graft-versus-host disease (GvHD) did not occur. Complete and partial responses were reported in one-half of patients, the majority of whom had no evidence of engraftment. Thirty-nine patients received transplants for leukemia. Transient engraftment was reported in 40% and two developed GvHD; survival extended to more than 2 years. The higher rate of engraftment in patients with leukemia suggests a role of pretransplant immune suppression. The risk of GvHD appears to be low despite complete HLA-mismatching. These data suggest a possible role for fetal liver transplantation in man. Future studies should probably be based on preclinical data obtained in large animal models.
Thymus 1987
PMID:Fetal liver transplantation in aplastic anemia and leukemia. 332 6

Balb/c nude mice were transplanted with cultured thymic fragments from C57BL/6, hybrid (C57BL/6xC3H F1 or BALB/cxC3H F1) or 2 separate strains simultaneously. Tolerance to H-2 of the thymus donor strain(s) was assessed by skin-graft acceptance and was seen in all cases except where 2 thymuses, each of differing strains, were transplanted simultaneously. Examination of mixed leukocyte culture and cell mediated lympholysis revealed blunted reactivity against thymus donor strains when skin graft tolerance was seen. Demonstration of a suppressor cell population was unsuccessful although a decreased cytotoxic T-cell potential was suggested by decreased GVH activity. These studies showed a unique dependence upon the thymus gland for the phenomenon demonstrated and are taken to be an example of a more generalized process in which effector cell function of the thymus is controlled by intrathymic events during the early maturation of precursor effector cells.
Thymus 1982 Feb
PMID:Transplantation of cultured thymus fragments. III. Induction of allotolerance. 646 Nov 9


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