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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)

Presented are experiences with the determination of immunosuppressive activity of alpha globulin fraction of human blood plasma, crude (Cohn fraction IV), partially purified and so-called low-molecular isolates of these substances. For testing the following techniques were used: the lymphocytotoxic and lymphoagglutination test, rosette-inhibition tests with human lymphocytes and splenocytes of mice immunized with sheep erythrocytes, lymphocyte blastic transformation inhibition test using PHA stimulated cells as well as in the mixed culture, inhibition of haemolytic plaque formation tests, determination of GVH reactivity using regional tests in the popliteal nodes, determination of HVG reactivity by skin graft survival test, determination of the effect on formation of precipitins against soluble antigens. The best results were obtained with the determination of survival times for skin grafts and the regional test in the popliteal nodes Fairly reproducible results were obtained in experiments on influencing the humoral antibody response and inhibition of formation of precipitating antibodies. Of in vitro methods tests of inhibition of lymphocyte blastic transformation both after PHA stimulation and in the mixed culture are applicable. Fully unsuitable proved the rosette, lymphocytotoxic and lymphoagglutination tests. In vitro modification of haemolytic plaque formation tests. In vitro modification of haemolytic plaque formation test is unfit for testing the crude fractions or partially purified drugs, its in vivo modification seems more feasible provided a large panel of animals is examined.
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PMID:Experiences with evaluation of immunosuppressive activity of alpha-globulin fraction of human blood plasma. 620 24

Using monoclonal antibodies to cell surface antigens and fluorescent cell sorter analysis, we studied peripheral blood lymphocyte subsets after bone marrow transplantation (BMT). In 13 patients studied 3 mo or more after BMT, the ratio of T-cell subsets defined by antibodies OKT4 and OKT8 was reversed (OKT4/OK%8 = 0.7 +/- 0.3) in comparison to normal volunteers or bone marrow donors (ratio OKT4/OKT8 = 1.7 +/- 0.4) (p less than 0.001). This reversed ratio persisted for up to 3 yr after BMT. In contrast to a previous report, presence of an abnormal ratio of T-cell subsets did not correlate with clinically significant graft-versus-host disease (GVHD). In agreement with a previous study, (26% +/- 8%; less than 4% in normals (p less than 0.001) and antibody OKT10 reactive cells (39% +/- 20% versus 10% +/- 4%) (p less than 0.01), suggesting in vivo activation. However, their PBL did not react with antibody B3/25 (antitransferrin receptor), a marker found on normal PBL after in vitro activation by mitogens (BMT patients less than 5%; normal PBL T cells plus PHA 45% +/- 11%). These results demonstrate that BMT patients have: (A) an abnormal ratio of T-cell subsets in the presence or absence of clinically significant GVDH disease so that these measurements were not useful in monitoring patients; (B) an increased number of T cells with cell surface phenotype (OKT8+, Ia+, OKT10+, B3/25-) that is distinct from normals but similar to patients with infectious mononucleosis or acquired hypogammaglobulinemia.
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PMID:Analysis of T lymphocytes after bone marrow transplantation using monoclonal antibodies. 628 11

Recipients of allogeneic bone marrow transplants are characterized by an immunodeficiency of varying intensity and duration. We have previously demonstrated the presence of in vivo activated suppressor T lymphocytes in immunodeficient patients with chronic graft-versus-host disease. To determine the basis of the immunodeficiency of transplant recipients early after transplantation, the lymphocytes of transplant recipients were analyzed phenotypically by E-rosette formation and staining with monoclonal antibodies (OKT-3, -6, and -8) and functionally by their blastogenic response to mitogens. Only 15% of transplant recipients' assays 0-3 months and 16% of assays 3-12 months following transplant were in the normal range. Transplant recipients during the first year after transplantation were characterized by an increased percentage (57%) of patients with a normal percentage of E-rosette-forming cells but reduced PHA responsiveness. In vitro coculture experiments demonstrated that their lack of PHA responsiveness was not due to the presence of in vivo activated suppressor cells or a decrease in mitogen-presenting cells. Staining with monoclonal antibodies revealed that the T lymphocytes from the majority of recipients at 0-3 months following transplantation contained a percentage of OKT8-positive cells greater than or equal to the percentage of OKT3-positive cells. This pattern (OKT8 greater than or equal to OKT3) was not found in the peripheral blood T lymphocytes of normal people but was found in 13 of 15 thymuses. Monoclonal staining with OKT6, a thymocyte-specific antibody, revealed positive staining of more than 10% of the peripheral blood leukocytes in the majority of recipients 0-3 months following transplantation, compared with only a few normals. We concluded that the circulating T lymphocytes of transplant recipients are phenotypically and functionally immature, and that their relative immaturity contributes to the transplant recipients' immunodeficiency.
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PMID:Immature T lymphocytes in the peripheral blood of bone marrow transplant recipients. 636 45

Immunologic evaluation of two unrelated male infants with clinical and laboratory evidence of severe combined immunodeficiency (SCID) revealed T cells with a mature phenotype in the peripheral circulation of both patients although both had biopsy evidence of thymic alymphoplasia. Both had a normal number of T cells with a cytotoxic/suppressor surface marker (OKT8) but very few T helper cells (OKT4). Lymphocyte stimulation with the mitogens PHA, Con A, and pokeweed or with allogeneic cells resulted in no proliferation. However, addition of T cell growth factor, plus the phorbol ester TPA, to lymphocytes cultured with the T cell mitogen PHA did result in some proliferation of T cells. In both cases these T cells demonstrated an XX female karyotype and were probably of maternal origin. In contrast, proliferating B cells stimulated with Epstein-Barr virus demonstrated a normal XY male karyotype. The possibility that severe combined immune deficiency in these patients was the result of graft-versus-host disease induced by maternal lymphocytes is discussed.
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PMID:XX T cells and XY B cells in two patients with severe combined immune deficiency. 660 7

Treatment of murine spleen cells with normal guinea pig serum selectively abrogated responsiveness of these cells to the T cell mitogens PHA or Con A, but failed to affect responses to LPS, i.e., a B cell-specific mitogen. Although pretreatment with GPS inhibited the in vitro immune response of mouse splenocytes to SRBC, responses were normal after restoration with T cells only, indicating that B cells had been spared by GPS. Consistent with these results, incubation with GPS resulted in the loss of reactivity of mouse lymphoid cells in MLC as well as CML systems, both of which test for T cell activities. Furthermore, parental spleen cells treated with GPS were no longer capable of inducing a GVH reaction in F1 hybrids. When compared, the effects of GPS and anti-Thy-1.2 antibodies plus C were found to be comparable. These results indicate that GPS can selectively remove a number of T cell functions from heterogeneous murine lymphoid cell suspensions. Since spleen macrophages were insensitive to GPS cytotoxicity, lack of T cell function is not likely to be due to depletion of these accessory cells.
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PMID:Selective removal of T cell function from mouse lymphocyte suspensions by treatment with normal guinea pig serum. 698 3

The properties of two antibiotics, cytostipin isolated from Penicillium stipitatum and vermiculine isolated from Penicillium vermiculatum, were examined in two systems for a rapid screening of current immunosuppressive agents [nucleolar test determining the degree of RNA synthesis in nucleoli of individual lymphocyte populations, and the reactivity of mouse lymphocytes to "T" (PHA) and "B" (LPS) mitogens]. Both antibiotics, distinctly suppressed the increase in number of "active" lymphocytes with compact nucleoli in the popliteal lymph node activated by SRBC. Incorporation of 3H-uridine into PHA-stimulated "T" lymphocytes was suppressed by both antibiotics, incorporation into LPS-stimulated "B" lymphocytes was inhibited by cytostipin but stimulated by vermiculine. The antibiotics were also tested in another two "classic" immune systems, the Jerne test and the GVH reaction. Both antibiotics in doses markedly inhibitory for GVH reaction did not suppress but significantly increased the number of the haemolytic plaques in spleens of SRBC-immunized mice.
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PMID:Immunosuppressive properties of the antibiotics cytostipin and vermiculine. 700 36

Following transplant, circulating immunoglobulin levels fell moderately and remained depressed less than 2 months for IgG, and for variable and longer periods of time for IgM and IgA. Repeated quantitative determinations of antibodies against multiple antigens did not show any decrease in the pretransplant levels. Indeed some patients developed herpes and cytomegalovirus infections to which they responded by a sharp increase in antibody titers. In 2 cases, a primary immunization was demonstrated (against CMV and BK virus) with increasing levels of IgM and IgG antibodies. Lymphocyte counts in peripheral blood returned to 500 mm# between day 10 and 29 (median day 18) and to pretransplant values within 6 weeks. Non specific stimulation of lymphocytes by mitogens in the immediate post-transplant period showed a decreased response to PHA and Con A, whereas the responses to pokeweek mitogens and alloantigens were only slightly diminished. The degree of the responses was related to the dose of cryopreserved marrow infused. We conclude that:--although the minimum dose for autologous bone marrow transplantation in man is around 0,5 10(8) nucleated bone marrow cells/Kg, much higher doses should be used to ensure faster and better restoration of immune reactivity.--The similarity of the immunological dysfunction following autologous and allogeneous bone marrow transplantation suggest that, in the immediate post-transplant period, the role of GVHD in cellular immunity depression may be minimal.
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PMID:[Studies of immunological status, following autologous bone marrow transplantation in man (author's transl)]. 700 23

Graft-versus-host disease (GvHD) after bone-marrow transplantation in dogs is controlled by many different genetic systems. In littermate combinations identical for the major histocompatibility complex (MHC) the number of systems that influence GvHD is related to the number of donor lymphocytes injected. If the number of donor lymphocytes administered is sufficiently low, minor histocompatibility systems do not influence survival after bone-marrow transplantation. With increasing numbers of donor lymphocytes the beneficial influence of MHC matching on GvH incidence and severity disappears and minor histocompatibility antigens, coded for on at least two other autosomal chromosomes as well as possibly the Y chromosome, can cause severe GvHD. In contrast, the X chromosome does not appear to carry a histocompatibility system that is of relevance to GvHD control. The severity and tissue distribution of histological signs of GvHD in recipients of bone-marrow and lymph-node cells from MHC-identical donors are similar to those in recipients of MHC-mismatched bone-marrow cells. Female donors do appear to cause severe GvHD more frequently than males. In contrast to rhesus monkey and human bone-marrow cells, dog bone-marrow cells are negative in PHA tests. This is in accordance with the generally benign course of GvHD in dogs that are treated with bone-marrow cells only from histocompatible littermate donors. The influence of the sex of the bone-marrow donor on GvHD incidence and severity is not reflected in differences between PHA tests with male and female dog lymphocytes. A better predictive test for GvH potential than the PHA test appears to be needed. Alternatives to additional donor selection for the prevention of GvHD in histocompatible recipients appear to be the use of a male donor and the removal of lymphocytes from bone-marrow-cell suspensions prior to transplantation.
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PMID:Alternatives to donor matching for control of graft-versus-host disease. 704 63

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

An unrelated donor bone marrow transplant (UD-BMT) was carried out on a 10-year-old patient with metachromatic leukodystrophy (MLD). We collected cerebrospinal fluid (CSF) on day +168 and cultured it with recombinant IL-2 and PHA-P to examine the origin of cells in the CSF. Analysis on variable number of tandem repeat (VNTR) of lymphocytes in the CSF amplified by PCR revealed that lymphocytes in the CSF were of donor origin. These data support that BMT at an early stage may prevent deterioration in MLD. Although the patient developed grade III acute GVHD with rash and diarrhea, we successfully treated acute GVHD using rabbit anti-human thymocyte immunoglobulin (ATG). UD-BMT may be an alternative treatment for patients with MLD in the absence of an HLA matched family donor.
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PMID:Detection of donor lymphocytes in the cerebrospinal fluid of a patient with metachromatic leukodystrophy following bone marrow transplantation. 774 47


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