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)

A panel of 34 clones was established from a cell line derived from the skin biopsy of a patient (genotype: A1, A2, B7, B8, DR3, DR6) undergoing acute graft-versus-host disease after semiallogeneic bone marrow transplantation with his mother's bone marrow (genotype: A1, A1, B7, B8, DR3, DR6). The T-cell line obtained presented the following phenotype: CD3+, CD4+, CD8-, CD16-, WT31+, T-cell receptor delta 1-, 4B4+, 2H4-, CD25+, DR+. This CD4+ T-cell line was poorly cytotoxic against the target cells tested, including the mother's phytohemagglutinin blasts as a negative control (autologous T cells), the father's phytohemagglutinin blasts bearing the mismatch haplotype, K562, U937, SVK14 (a keratinocyte cell line), and a panel of B-lymphoblastoid cell lines bearing HLA-A2, the known mismatch antigen. All but 1 of the 34 clones obtained were of CD4+ phenotype, and none was CD16+. Only the sole CD8+ clone showed significant cytotoxicity against the father's phytohemagglutinin blast; however, this cytotoxic activity was associated with the highest score for nonspecific killing against both K562 and U937. This work demonstrates the feasibility of obtaining a large panel of clones from a graft-versus-host disease target organ to constitute the basic cellular material for in vitro study of the graft-versus-host process.
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PMID:Characterization of skin-infiltrating T lymphocytes during acute graft-versus-host disease. 224 50

A male patient with severe aplastic anemia who had rejected a first T cell depleted graft from his HLA-identical sister was retransplanted from the same donor without T cell depletion and using an intensified conditioning regimen. After 8 weeks acute graft versus host disease (GVHD) developed and peripheral blood mononuclear cells (PBMC) were obtained. After in vitro restimulation and following limiting dilution cloning, 15 proliferative (PLT) and 25 cytolytic (CTL) T cell lines specific for host PBMC but unreactive to donor PBMC were isolated. Only 1 of 10 clones which could be expanded sufficiently for testing recognized a target cell (haploidentical sister), and in only 4 instances could a restriction element be found in a panel study (3 times HLA-A2; once HLA-BW49) of 13 unrelated stimulators. Of the 8 CTL clones testable after expansion, none showed a clear restriction and none recognized any of the family cells. Our data demonstrate that anti-patient reactive PLT and CTL lines can be found in PBMC. In no instance was segregation with HLA found. Only HLA-class I restriction was detectable.
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PMID:[In vivo detection of alloreactive T cells of the donor in graft versus host disease]. 354 Nov 72

Using immunohistological techniques, the cellular composition of lymph nodes was assessed in 18 patients who had died 15 to 326 days after allogeneic bone marrow transplantation for leukaemia. The lymph nodes showed reduced cellularity of the cortex and paracortex, dilated sinuses and no lymphoid follicles. The majority of leucocytes were T lymphocytes with an inversion of the normal T4:T8 ratio. No cells were detected expressing immature cortical thymocyte antigens, using NA1/34 and OKT10, but an excess of T11 (E rosette receptor)+ cells over the sum of T4+, T8+ and HNK1+ cells raised the possibility of the presence of immature cells. B lymphocytes were extremely rare and present as clusters in only two patients. Despite this, plasma cells were prominent in many cases and their number increased with time post transplant. The predominant immunoglobulin heavy chain class was IgA in seven cases, IgG in three cases, IgM in two cases and IgE in one case with no relationship between dominant class and days post transplant. In patients with graft-versus-host disease (GvHD), there was a significantly lower T4:T8 ratio but no increase in expression of lymphocyte activation markers. Pyknotic leucocytes were present in half of the cases with GvHD and none of the other cases. No differences were detected in patients who had received marrow purged with monoclonal antibodies (Campath-I or UCHT1). Chimeric studies on three recipients of one haplotype matched marrow, using a monoclonal antibody specific for HLA-A2 and A28 antigens, showed a significant influx of donor cells by 56 days but this did not appear to be an immediate prelude to full morphological reconstitution.
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PMID:The cellular composition of human lymph nodes after allogenic bone marrow transplantation: an immunohistological study. 354 75

Skin biopsies from 3 patients receiving one-haplotype-matched bone marrow grafts have provided a unique opportunity to demonstrate the presence of donor cells in situ using immunohistological techniques and a monoclonal antibody directed against an epitope common to HLA-A2 and HLA-A28 antigens. The infiltrating cells were also analyzed in consecutive tissue sections with a panel of monoclonal antibodies to human leukocyte antigens, T cells, and epidermal Langerhans cells. Most of the infiltrating cells were shown to be T lymphocytes of donor origin, regardless of whether the histological changes were consistant with graft-versus-host disease (GVHD) or were eczematous. Donor T cells were also shown to colonize histologically normal skin soon after transplantation. Epidermal keratinocytes, dermal endothelium, and adnexal structures did not express the donor HLA type (i.e., were host derived) but the origin of the epidermal Langerhans cells could not clearly be established. The data show that donor cells preferentially migrate to certain sites in skin after transplantation and are not always associated with GVHD.
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PMID:Chimerism in skin of bone marrow transplant recipients. 620 58

Minor histocompatibility antigen disparities between human leukocyte antigen (HLA)-matched bone marrow donors and recipients are a major risk factor for graft versus host disease (GVHD). An HLA-A2.1-restricted cytotoxic T cell clone that recognized the minor histocompatibility antigen HA-2 was previously isolated from a patient with severe GVHD after HLA-identical bone marrow transplantation. The HLA-A2.1-bound peptide representing HA-2 has now been identified. This peptide appears to originate from a member of the non-filament-forming class I myosin family. Because HA-2 has a phenotype frequency of 95 percent in the HLA-A2.1-positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation.
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PMID:Identification of a graft versus host disease-associated human minor histocompatibility antigen. 753 51

HLA-identical bone marrow transplantation (BMT) may be complicated by graft-versus-host disease or graft rejection. Both complications are thought to be initiated by recognition of minor histocompatibility (mH) antigens by HLA-restricted mH-antigen-specific T lymphocytes. Using HLA-A2-restricted mH antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were investigated were recognized by the HA-1-, -2-, and -4-, and HY-specific CTL clones, their BMMNCs and HPCs were recognized as well by these CTL clones, resulting in antigen-specific growth inhibition of erythrocyte burst-forming units (BFU-E), colony-forming units-granulocyte (CFU-G), and CFU-macrophage (CFU-M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from four donors to a lesser extent than from two other donors. We further investigated whether inhibitory cytokines released into the culture medium by the antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for suppression of HPC growth or whether this effect was caused by direct cell-cell contact between CTLs and HPCs. HPC growth inhibition was only observed after preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in semisolid HPC culture medium. When no cell-cell contact was permitted before plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2 blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct cell-cell contact between target cells and CTLs and were not caused by the release of inhibitory cytokines into the culture medium by antigen-specific stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen-specific CTLs can inhibit HPC growth by a direct cytolytic effect and may therefore be responsible for BM graft rejection after HLA-identical BMT.
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PMID:Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact. 826 Jul 14

A patient with acute leukemia and her family including four HLA-identical siblings were analyzed to select a donor who was not only HLA- but also minor histocompatibility (mH) antigen compatible for allogeneic bone marrow transplantation (BMT). The HLA-A2 restricted mH antigen-specific HA-1, -2, -4, and -5 cytotoxic T-lymphocyte (CTL) clones were used to type the family members for expression of these mH antigens. The patient and one HLA-identical sibling were compatible for these mH antigens. This sibling was selected as the bone marrow donor. The patient engrafted promptly but developed acute and chronic graft-versus-host disease. To study the presence of other mH antigen disparities between recipient and donor, host-versus-graft CTL lines and clones were generated by stimulation of recipient peripheral blood lymphocytes (PBLs) with donor bone marrow cells, and graft-versus-host CTL lines were generated after BMT by stimulation of PBLs of donor origin with recipient bone marrow cells. These CTL lines were cytotoxic to cells from the bone marrow donor and from the recipient, respectively, and to cells from several other family members. T-cell lines, generated from the patient after BMT by stimulation of recipient-derived PBLs with donor bone marrow cells, exhibited no specific cytotoxicity to donor or recipient cells. Chimerism studies after BMT revealed that the PBLs and T-cell lines generated after BMT were of donor origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple minor histocompatibility antigen disparities between a recipient and four HLA-identical potential sibling donors for bone marrow transplantation. 830 Apr 7

To study the repertoire and specificity of T lymphocytes infiltrating skin lesions during graft-versus-host disease (GVHD), we performed an exhaustive molecular and functional analysis of 146 T-cell clones derived from the skin of three patients undergoing an acute GVHD after allogeneic bone marrow transplantation (BMT) from HLA-mismatched related donors. Analysis of T-cell receptor (TCR) rearrangement and TCR chain junctional sequences demonstrated the presence of 11 distinct clones among the 64 derived from patient UPN1, six among the 58 derived from patient UPN2, and seven among the 24 derived from patient UPN3. Three of the 11 T-cell clones from patient UPN1, and all clones from patients UPN2 and UPN3 reacted with mismatched HLA alleles between the bone-marrow donor and recipient. Moreover, both HLA class I (HLA-A2 and -B27) and class II (HLA DP101, DP401, DP1301, DQ8, and DR402) molecules were recognized during this early antihost response. Finally, both TCR alpha and beta chains turned out to be extremely diverse, even within populations of clones derived from the same patient and directed against the same HLA allele. Taken together, these results indicate that any HLA mismatch is potentially targeted during early GVHD, and that the T-cell response at the onset of GVHD is both oligoclonal and highly diversified.
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PMID:HLA-target antigens and T-cell receptor diversity of activated T cells invading the skin during acute graft-versus-host disease. 863 Mar 97

The pathogenesis and clinical features of chronic graft-versus-host disease (cGVHD) resemble those of several autoimmune diseases, as evidenced by frequent dermal, hepatic, occular, oral, pulmonary, gastrointestinal and neuromuscular involvement. Serosal involvement, however, has only rarely been reported and most of the existing accounts are historical. We describe a boy transplanted in third CR of CALLA-positive ALL from his HLA-identical sister who developed cGVHD, which was complicated by a huge pericardial effusion as a part of severe polyserositis including pleural effusion, ascites, and polyarthritis. The patient shared the HLA antigens HLA-A2, B51, and DQW6 which are associated with autoimmune diseases.
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PMID:Massive pericardial effusion complicating the course of chronic graft-versus-host disease (cGVHD) in a child with acute lymphoblastic leukemia following allogeneic bone marrow transplantation. 938 88

Cytotoxic T lymphocytes (CTL) specific for human minor histocompatibility (H) antigens can be isolated from the blood of major histocompatibility complex (MHC)-matched allogeneic bone marrow transplant (BMT) recipients and may play a prominent role in the graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactions (Tsoi et al, J Immunol 125:2258, 1980; Tsoi et al, Transplant Proc 15:1484, 1983; Goulmy et al, Nature 302:159, 1983; Irle et al, Transplantation 40:329, 1985; and Niederwieser et al, Blood 81:2200, 1993). The identification of minor H antigens that are expressed in hematopoietic cells, including leukemic cells, but not in fibroblasts and other tissue types has suggested that such tissue-restricted antigens could potentially serve as targets for T-cell immunotherapy to enhance GVL activity without inducing GVH disease (de Bueger et al, J Immunol 149:1788, 1992; van der Harst et al, Blood 83:1060, 1994; and Dolstra et al, J Immunol 158:560, 1997). To explore the feasibility of this strategy, donor CD3+CD8+ CTL clones specific for recipient minor H antigens were isolated and characterized from allogeneic BMT recipients. CTL clones were obtained from the majority of donor/recipient pairs. Seventeen distinct minor H antigens distinguishable by their MHC-restricting allele, population frequency, and/or distribution of tissue expression were defined by 56 CD3+CD8+ CTL clones isolated from these patients. The MHC-restricting alleles for these CTL clones included HLA-A2 and HLA-B7, which had previously been shown to present minor H antigens to CTL, as well as HLA-A3, -A11, -B8, -B53, and -Cw7, which had not previously been described to present minor H antigens to CTL. Estimated phenotype frequencies for these 17 distinct minor H antigens range from 0.17 to 0.92. In vitro cytotoxicity assays using hematopoietic cells and fibroblasts as target cells showed that 5 of the 17 minor H antigens were expressed in both hematopoietic cells and fibroblasts. However, 12 were presented for CTL recognition only by hematopoietic cells and not by dermal fibroblasts derived from the same donors. These results significantly extend the spectrum of CTL-defined human minor H antigens that could potentially serve as target antigens for cellular immunotherapy to promote GVL activity after allogeneic BMT.
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PMID:Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution. 949 Jul 9


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