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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)

The liver is a major target organ of graft-versus-host disease. We have induced graded intensities of acute GVHD to minor histocompatibility antigens in a well-characterized murine bone marrow transplant model and analyzed hepatic pathology one month after BMT. Nuclear-magnetic-resonance relaxation times and proton spectra were compared to systemic clinical disease, serum biochemistries, and histologic findings. T2 relaxation times correlated directly with the intensity of histologic abnormalities, but the hepatic histology remained mild even in animals with moderate GVHD. In contrast, NMR proton spectra of hepatic tissue showed large decreases in metabolite levels (acetate and glycogen) in animals with moderate systemic disease despite mild hepatic histology. We conclude that NMR of the liver can be used to differentiate hepatic from systemic GVHD in this model and may help to elucidate the differential effects of GVHD in various target organs.
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PMID:Nuclear magnetic resonance of hepatic graft-versus-host disease in mice. 225 43

The aim of this study was to test whether colony stimulating factors (CSF) and other cytokines facilitate the recovery of a variety of immunohematopoietic functions in lethally irradiated mice undergoing bone marrow transplantation (BMT). Two experimental systems were employed: (a) lethally irradiated mice transplanted with syngeneic or T cell-depleted semi-allogeneic bone marrow (BM) cells (0.1-10 x 10(6)), subsequently treated by multiple doses of cytokines; and (b) lethally irradiated mice transplanted with BM cells that had previously been cultivated with cytokines. The cytokines used were: pure natural mouse interleukin-3 (IL-3); recombinant mouse granulocyte-macrophage CSF (rGM-CSF); recombinant human interleukin-2 (rIL-2); and crude cytokine preparations obtained from the culture supernatants of murine leukemia WEHI-3b cells (containing mainly IL-3), and of phorbol myristate acetate (PMA)-stimulated EL4 leukemia cells and concanavalin A-stimulated rat splenocytes (each containing a multitude of cytokines). For BM cultures (1-9 days), the cytokines were used at a dosage of 1-100 U/ml; for in vivo treatment, 2 x 10(2)-5 x 10(4) units were administered intraperitoneally and subcutaneously at different schedules for varying periods (1-3 weeks). The following parameters were tested 1-10 weeks post-BMT: white blood cell count, colony formation in agar and in the spleen of lethally irradiated mice, proliferative responses to mitogens and alloantigens, allocytotoxicity and antibody production (serum agglutinins and plaque-forming cells) against sheep red blood cells. Under appropriate conditions, cytokine treatment either in vitro or in vivo significantly enhanced (2- to 50-fold compared with controls) most functions tested at 2-8 weeks post-BMT, and shortened the time interval required for full immunohematopoietic recovery by 2-5 weeks. In recipients of semi-allogeneic, T lymphocyte-depleted BM no evidence of graft-versus-host disease was found. It is suggested that judicious application in vitro and/or in vivo of certain pure cytokines (e.g. GM-CSF, IL-3) or cytokine 'cocktails' might be beneficial in enhancing hematopoiesis and in the treatment of immunodeficiency associated with BMT.
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PMID:In vitro and in vivo cytokine-induced facilitation of immunohematopoietic reconstitution in mice undergoing bone marrow transplantation. 304 95

Upon activation, B cells express growth and differentiation receptors that permit them to proliferate and differentiate. The aim of this study is to define the nature of the intrinsic B cell defects found in marrow recipients using assays for B cell activation, proliferation, and differentiation. B cells from five short-term (less than three months postgrafting) and 15 long-term (greater than one year postgrafting) marrow recipients (ten with and five without chronic graft-v -host disease [GVHD]) were studied. T cell supernatants (T-sup) were prepared by stimulating normal T cells with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and phytohemagglutinin. Highly purified B cells were used to assess B cell proliferation responses to T-sup after Staphylococcus aureus Cowan I (SAC) activation and for B cell immunoglobulin production responses to T-sup stimulation after SAC activation. B cells from all five short-term patients and one long-term patient with chronic GVHD did not respond to any stimulation. B cells from two patients with chronic GVHD responded to SAC but had decreased proliferative and differentiative responses to T-sup. B cells from three of seven patients with chronic GVHD and two of five long-term healthy patients could proliferate but could not secrete immunoglobulin in response to SAC plus T-sup stimulation. Furthermore, there was a significant correlation between serum IgG and/or IgM in marrow recipients and the differentiative responses of their B cells to T-sup (P = 0.0075, Fisher's Exact). B cell defects occur at various stages of maturation postgrafting. These defects include the failure to respond to the SAC activation signal, the failure to proliferate in response to T-sup, and the failure to differentiate in response to T-sup. These findings are probably due to the inability of B cells from certain marrow recipients to undergo a second round of ontogeny.
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PMID:Proliferative and differentiative responses of B cells from human marrow graft recipients to T cell-derived factors. 353 29

Histologic, histochemical, and histoenzymatic investigations of nine cases of Omenn's disease showed generalized lymphoid depletion, including B cells and all T-cell subpopulations; an apparent proliferation of alpha-naphthyl acetate esterase-, acid phosphatase-, OKM1-positive macrophages and T6 interdigitating cells; a thymic hypoplasia with arrest of hassallian epithelial maturation; starlike fibrinous deposits in the bone marrow; and extensive cutaneous lesions characterized by hyperkeratosis, apoptotic cell death associated with the intraepidermal presence of T4+ and T8+ cells, localized necrosis of the basement membrane, expression of Ia antigens by malpighian cells, and progressive loss of the T6+ Langerhans' cells. These lesions, mainly the skin and bone marrow changes, are reminiscent of those observed in acute graft versus host reaction. Although a blood chimerism has never been demonstrated, these pathologic observations support the hypothesis of graft versus host disease in a primary cellular immunodeficiency and the persistence of the proliferating maternal cells in the peripheral target organs.
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PMID:Omenn's syndrome--pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases. 367 86

The effect of irradiation on neutrophil oxidative function was evaluated using a flow cytometric assay of intracellular hydrogen peroxide (H2O2) production. This assay quantitates the H2O2-dependent conversion of the nonfluorescent compound, 2'-7'-dichlorofluorescein (DCFH), into fluorescent 2'-7'-dichlorofluorescein (DCF) on a single-cell basis. Intracellular H2O2 production in response to stimulation with phorbol myristate acetate was not affected by neutrophil irradiation at doses up to 2500 rad. In addition, irradiation of intracellular DCFH and aqueous 2'-7'-dichlorofluorescein diacetate (DCFH-DA) resulted in DCF production, which suggested that oxidative molecules produced by aqueous radiolysis were detected by this assay. This study indicates that radiation doses of 1500 to 2500 rad, which are sufficient to prevent induction of graft-versus-host disease by transfused blood components, are not deleterious to neutrophil oxidative metabolism.
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PMID:Oxidative product formation in irradiated neutrophils. A flow cytometric analysis. 382 75

The inflammation-associated molecules intercellular adhesion molecule (ICAM)-1, endothelial lymphocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1, human leukocyte antigen (HLA)-DR, interleukin (IL)-2R (CD25), CD34, alpha-1-antichymotrypsin (alpha 1-ACT), and L1 antigen were studied in skin from marrow recipients to determine the timing and distribution of their expression in relation to the clinical and histologic evolution of graft-versus-host disease (GvHD). Four phases were recognized: 1. pretransplant with no immunohistologic change; 2. posttransplant with no evidence of GvHD when dermal alpha 1-ACT + macrophages were increased; 3. posttransplant with clinical, but not histologic, evidence of GvHD with increased keratinocyte HLA-DR and ICAM-1 expression and increased numbers of VCAM-1+ dermal cells; and 4. posttransplant with clinical and histologic evidence of GvHD characterized by an infiltrate of CD25+ T cells, L1+, alpha 1-ACT+ and VCAM-1+ macrophages, L1 antigen expression on keratinocytes accompanied by further increases in HLA-DR and ICAM-1, and increased endothelial ELAM-1 staining with a reciprocal decrease in CD34. A sequential accumulation of cellular and molecular changes, therefore, occurs in the evolution of acute GvHD, and immunostaining for HLA-DR, ICAM-1, and VCAM-1 may be helpful in diagnosing early disease.
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PMID:A prospective study of cellular and immunologic changes in skin of allogeneic bone marrow recipients. Relationship to clinical and histologic features of acute graft-versus-host disease. 817 66

Highly purified CD4+ CD45RA+ cells from cord blood and peripheral blood from healthy adults were studied. The levels of expression of the CD2, CD3, CD4 and CD28 antigens were similar; however, CD45 and CD45RA antigen expression were slightly lower in cord cells. The reduced expression of the CD45RA antigen on cord CD4+ T cells was confirmed in whole blood. Functional assessment revealed deficiencies in cord CD4+ CD45RA+ T cells. Interleukin-2 (IL-2) production in response to specific triggering via CD2 monoclonal antibody (mAb) alone, or CD2 mAb in combination with CD28 mAb showed marked underproduction (about 10% of adult production). When CD25 expression was examined, it was observed that the proportion of activated CD4+ CD45RA+ T cells in cord blood was lower than in adult (about 20% of adult expression). Proliferation to CD2 mAbs or CD2 + 28 mAbs of cord blood native cells was similarly depressed. Investigation of IL-2 mRNA expression under these stimulatory conditions paralleled the results observed for CD25 expression, IL-2 production and proliferation. When phorbol 12-myristate 13-acetate (PMA) was added to the cells triggered with CD2 + 28mAbs, the responses examined were enhanced in both cord and adult blood with no significant differences between the groups. These findings suggest that under identical conditions of stimulation, purified cord blood CD4+ CD45RA+ T cells do not acquire similar activation status as their adult counterparts. These findings may help in understanding the reduced graft-versus-host disease (GVHD) observed in cord blood stem cell transplantation.
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PMID:Cord blood CD4+ CD45RA+ T cells achieve a lower magnitude of activation when compared with their adult counterparts. 915 47

A deficiency of neonatal T lymphocytes to express CD154 antigen in response to ionomycin and phorbol 12-myrsistate 13-acetate (PMA) stimulation or after CD3 cross-linking has been described. In the present report we describe that CD45RA+ newborn cells are able to synthesize and express CD154 at similar or even higher levels than adult cells in response to ionomycin and cAMP-elevating agents which trigger the protein kinase A (PKA) -mediated metabolic pathway. Peak CD154 protein concentrations in newborn cells were found between 4 and 8 hr after stimulation with ionomycin and dibutyryl cAMP. These agents, however, did not induce expression of the early activation antigen CD69. Surface levels of CD154 did not correlate with specific mRNA concentration, indicating that dibutyryl cAMP up-regulates CD154 by acting at a post-transcriptional stage. The CD154 antigen induced by PKA activation of newborn cells was functional, since upon binding to CD40 on B lymphocytes in the presence of interleukin-4 (IL-4), it promoted immunoglobulin heavy-class switching to IgE. We also found a different pattern of cytokine production between neonatal and adult CD4+ T cells. In response to ionomycin and dibutyryl cAMP, cord blood cells were more prone than adult lymphocytes to secrete the T helper type 2-derived immunosuppressive cytokines IL-4 and IL-10. Taking into account that the feto-maternal environment is rich in cAMP-elevating agents, the reduced risk of graft versus host disease associated with cord blood trasplantation, as compared with the risk with adult bone marrow cell transplants, may be due to the bias of neonatal cells to differentiate towards the T helper type 2 functional cell subset.
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PMID:Induction of functional CD154 (CD40 ligand) in neonatal T cells by cAMP-elevating agents. 1092 69

This report describes the use of octreotide, a synthetic somatostatin analogue, for severe diarrhea caused by acute intestinal graft-versus-host disease (GVHD) after bone marrow transplantation. A 22-month-old boy suffered grade 4 intestinal GVHD, with profuse diarrhea, intestinal inflammation, and grossly bloody stools after matched, unrelated donor transplant for biphenotypic leukemia. He required intensive blood product support. In addition to aggressive anti-GVHD therapy, octreotide acetate was initiated at 30 microg (2 microg/kg) intravenously 3 times per day and escalated to continuous infusion at 15 microg/hr (1 microg/kg per hour). The diarrhea did not improve with anti-GVHD treatment. However, moderate dose octreotide therapy resulted in prompt control of the bloody diarrhea, which rebounded on cessation of octreotide therapy. Rebound diarrhea responded promptly when the dose of octreotide was escalated. Octreotide was associated with an exacerbation of preexisting hypertension, but it appeared to be effective for control of severe, bloody diarrhea caused by acute GVHD in a child, with manageable side effects. Further studies of this application in infants and children are warranted.
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PMID:Continuous octreotide infusion for the treatment of secretory diarrhea caused by acute intestinal graft-versus-host disease in a child. 1095 6

Treatment with 8-methoxypsoralen plus ultraviolet A radiation and extracorporeal photochemotherapy (photopheresis) are widely used for the treatment of psoriasis and other inflammatory skin diseases, graft-versus-host disease, and mycosis fungoides. As the ratio of Th1 and Th2 cells appears to be critical for pathogenesis and progression of these disorders the effect of psoralen plus ultraviolet A on Th1 and Th2 cytokine production by CD4+ lymphocytes was investigated. Human peripheral blood lymphocytes were incubated in the presence of anti-CD3, rh-IL2, and rh-IL4 for 48 h. After subsequent stimulation with rh-IL2 and rh-IL4 for 72 h cells were treated with 8-methoxypsoralen (100, 500, 1000 ng per ml) plus ultraviolet A (2 J per cm2) and incubated for a further period of 5 h in the presence of ionomycine, phorbol-12-myristate acetate and monensin. Fluorescence-activated cell sorter analysis revealed a significant reduction of interleukin-2- and interferon-gamma-producing CD4+ cells upon psoralen plus ultraviolet A treatment depending on the concentration of 8-methoxypsoralen. In contrast, interleukin-4-producing CD4+ cells were increased, indicating a shift from Th1 to a Th2 cell cytokine profile upon psoralen plus ultraviolet A treatment. These results indicate that 8-methoxypsoralen photochemotherapy of lymphocytes is able to modulate their Th1/Th2 distribution. Inhibition of Th1 cytokine expression by psoralen plus ultraviolet A might help to explain its beneficial effects in the treatment of Th1 dominated skin diseases.
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PMID:Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen plus ultraviolet A radiation induces a shift in cytokine expression from a Th1 to a Th2 response. 1123 22


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