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)

MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice.
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PMID:MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells. 145 84

The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground-glass pattern in early pneumonia (n = 5); a peripheral distribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis.
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PMID:Intrathoracic complications following allogeneic bone marrow transplantation: CT findings. 188 25

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.
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PMID:Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. 311 64

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.
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PMID:Bone marrow transfers in X-irradiated mice congenic at the lpr locus: some paradoxical effects. 331 28

Azimexon, a 2-cyan-aziridinyl immune modulator, was given at a dose of 250 mg/m2/day for 10 days IV to 12 patients with AIDS and 16 with AIDS related complex (ARC). A decrease in total number of AIDS related symptoms from 43 to 24 and in mean number from 2.6 to 1.5 was observed among ARC patients (p less than .01). The most commonly improved symptoms were diarrhea, fatigue, and weight loss with the least frequently improved being lymphadenopathy. The following improvements in immune parameters were observed among ARC patients. DTH to recall antigens improved with an increase in number of positive tests from 35 to 47 and in mean number of positive skin tests from 2.2 on day 0 to 2.9 on day 14 (P less than .05). The geometric mean of the absolute lymphocyte count was 1.395 X 10(3)/microliter on day 0 with a significant increase of 18.0 percent on day 5 (P less than .01) and a 7.7 percent increase on day 21. The geometric mean of the OKT4+ cells on day 0 was 0.250 X 10(3)/microliter with a 33.3 percent increase on day 5 (P less than .07) and a 14.1 percent increase on day 21. T4/T8 ratio increased by 32.7 percent on day 5 (P less than .05) and by 19.4 percent on day 21 from an initial geometric mean of 0.339 X 10(3)/microliter on day 0. The geometric mean of GVH responses increased by 18.2 percent on day 5 (P less than .05) and by 24.0 percent on day 21 (P less than .07) from an initial value of 41.04 mm3. No symptomatic or immunologic improvements were observed among AIDS patients, but rather a significant decrease in mitogenic responses. PHA responses decreased by 70.3 percent on day 5 (P less than .05) and 42.2 percent on day 21 from an initial geometric mean of 4.02 X 10(3) cpm/10(3). Con-A responses decreased by 75.1 percent on day 5 (P less than .05) and increased by 20.3 percent on day 21 from an initial value of 1.14 X 10(3)/10(5) cells. Pretreatment number of absolute OKT4+ cells was the most significant prognostic survival variable. Thus, 8/9 patients with less than 0.10 X 10(3) OKT4+ blood cell/microliter subsequently died as compared to only 1/17 with greater than or equal to 0.10 X 10(3) OKT4+ cells (p less than .001). The only toxic effect of this treatment was mild hemolysis which disappeared upon cessation of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of azimexon therapy on host defense parameters and disease-associated symptoms in the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). 375 9

By induction of a graft-vs.-host reaction (GVHR) in nonirradiated H-2-different F1 mice, one can induce stimulatory pathological symptoms, such as lymphadenopathy and hypergammaglobulinemia, combined with the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). Alternatively, the GVHR can lead to the suppressive pathological symptoms, such as pancytopenia and hypogammaglobulinemia, characteristic of acute GVH disease (GVHD). Whether stimulatory or suppressive symptoms are induced by a GVHR depends, in our view (2-4), on the functional subset of donor T cells activated in the F1 host. The purpose of the present study was to investigate whether class I and/or class II H-2 alloantigens can selectively trigger, out of a pool of unselected donor T cells, those subpopulations of T cells responsible for the stimulatory and suppressive GVH symptoms, respectively. For the induction of the GVHR, 10(8) lymphoid cells from C57BL/6 (B6) donors were injected into three kinds of F1 hybrid mice, which had been bred from H-2 mutant strains on a B6 background. Whereas the I-A-disparate (B6 X bm12)F1 recipients exclusively developed stimulatory GVH symptoms, including SLE-like autoantibodies and immune complex glomerulonephritis, the K locus-disparate (B6 X bm1)F1 recipients showed neither clearly stimulatory nor clearly suppressive GVH symptoms. In marked contrast, the (bm1 X bm12)F1 recipients, which differ from the B6 donor strain by mutations at both K and I-A locus, initially developed stimulatory GVH symptoms, but rapidly thereafter showed the suppressive pathological symptoms of acute GVHD and died. Moreover, spleen cells obtained from (B6 X bm12)F1 mice injected with B6 donor cells helped the primary anti-sheep erythrocyte (SRBC) response of normal (B6 X bm12)F1 spleen cells in vitro, whereas spleen cells (bm1 X bm12)F1 mice injected with B6 donor cells strongly suppressed the primary anti-SRBC response of normal (bm1 X bm12)F1 spleen cells. Spleen cells from the K locus-disparate (B6 X bm1)F1 recipients also suppressed the primary anti-SRBC of normal (B6 X bm1)F1 spleen cells; this suppression, however, was weak when compared with the suppression induced by spleen cells from GVH (bm1 X bm12)F1 mice. Taken together, these findings indicate that a small class II (I-A) antigenic difference suffices to trigger the alloreactive donor T helper cells causing SLE-like GVHD. In contrast, both class I (H-2K) and class II (I-A) differences are required to trigger the subsets of donor T cells responsible for acute GVHD. It appears that alloreactive donor T helper cells induce the alloreactive T suppressor cells, which then act as the suppressor effector cells causing the pancytopenia of acute GVHD. These findings may help to understand the variability of GVH-like diseases caused by a given etiologic agent, their cellular pathogenesis, and association with certain HLA loci.
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PMID:Allosuppressor and allohelper T cells in acute and chronic graft-vs.-host disease. II. F1 recipients carrying mutations at H-2K and/or I-A. 621 18

Graft versus host disease (GVHD) is a well recognized entity following bone marrow transplantation. Similar syndromes have been described after blood product transfusions, notably in patients with primary immunodeficiency syndromes and in patients with malignancies associated with immune deficiency or under immunosuppressive treatment. Review of the literature shows that posttransfusion GVHD is characterized by maculopapular skin rash, gastro-intestinal symptoms, liver disease, severe pancytopenia and, in some cases, hepatosplenomegaly and lymphadenopathy. The time to onset and the duration of the disease are short (10 days) and the mortality approaches 90%. The clinical features of this rare disorder are presented in the hope that, with increased awareness of this complication, clinicians will take preventive measures in patients at risk because no satisfactory therapy yet exists.
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PMID:[Clinical characteristics and evaluation of risk in the graft versus host reaction following transfusion]. 663 42

Graft-versus-host disease developed in two dogs injected with lymphocytes from BCG immunized donors. The disease was characterized by bone marrow depression, ulcerative enteritis, necrotizing cholangiohepatitis, thymic atrophy, pancreatitis, lymphadenopathy, inflammation of mucous membranes and weight loss. In one of the two dogs repopulation of bone marrow and lymphoid tissue by donor cells was demonstrated by cytogenetics. The development of GVHD was considered unusual because both animals received on immunosuppressive treatment and both responded well to PHA in lymphocyte transformation assays indicating they were immunocompetent. It was hypothesized that stimulation of donor lymphocytes by BCG enhanced their ability to induce a graft-versus-host reaction.
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PMID:Graft-versus-host disease in two immunocompetent dogs. 746 Oct 47

A hybridoma (F6C7) was established by fusing NS1 cells with spleen cells of MRL/Mp-+/+ (MRL/+) mice suffering from lpr-GVHD. This F6C7 mAb (IgG2b, kappa) stains a broad spectrum of blood cells at varying intensities in mice and rats. In normal (BALB/c) mice, granulocytes and B cells are highly positive for F6C7-reactive Ag (F6C7-Ag). Thymocytes and peripheral (CD4+ and CD8+) T cells show negative to low intensities. These staining profiles are similar in C57BL/6, AKR/J, C3H/HeJ, and MRL/+ mice. When spleen cells were activated in vitro, a blastic cell population of autoactivated CD4+ and CD8+ T cells showed increased F6C7-Ag expression. Alloactivated CD4+ blastic T cells also showed increased expression of F6C7-Ag, whereas alloactivated CD8+ blastic T cells as well as Con A-activated CD4+ and CD8+ blastic T cells remained at the level of small (nonblastic) cells. These findings suggest that the surface expression of F6C7-Ag is up-regulated in some activation processes of T cells, particularly in autoactivation. Young (2-month-old) MRL/Mp-lpr/lpr (MRL/lpr) mice show staining profiles of F6C7-Ag similar to those of normal mice, except that many more blastic (CD4+ and CD8+) T cells show high F6C7-Ag expression than those of normal mice. A small but significant number of CD4+F6C7-Ag(high) and a much higher number of CD8+F6C7-Ag(high) blastic T cells were observed in the spleen cells of MRL/+ mice suffering from lpr-GVHD. These blastic T cells may exert autoreactivity and participate in the initiation of autoimmune diseases, lymphadenopathy, and lpr-GVHD. Immunoprecipitation and SDS-PAGE revealed that F6C7-Ag is a heterodimer comprised of approximately 78- and 70-kDa molecules without disulfide bonds.
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PMID:Increased cell surface expression of a newly identified heterodimer on activated blastic T cells. 811 79

We report the case of a patient with chronic lymphocytic leukemia (CLL) with persistent lymphocytosis and lymphadenopathy after allogeneic bone marrow transplantation (BMT). After receiving a donor lymphocyte infusion on day 87 he achieved complete remission upon development of chronic graft-versus-host disease, suggesting that a graft-versus-leukemia effect is operative in this malignancy.
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PMID:Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. 887 40


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