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)

Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ-induced PLN response in mice. The GVH reaction was induced locally by sc injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte subsets were monitored during the onset of the GVH reaction by flow cytometry and immunophenotyping. Examination of cell size and chromatin decondensing for T- and B-cell subsets showed differences in activation profile during the early phase of the GVH reaction. The present study provides direct evidence for early in vivo activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T-cell activation in the induction of a GVH reaction and suggest that recirculatory host B-cells can play an important role in early GVH node enlargement. Overall, our comparative analysis supports the concept of polyclonal T-cell activation for both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced lymphoproliferation leading to autoimmune reactions is a challenging issue. A number of drugs and chemicals have been tested in the PLNA assay for lymphoproliferative potential. We previously reported the activation and proliferation of T-cell subsets following STZ injection into murine footpads. The STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell subsets were postulated to be similar to those of an acute allogeneic GVHR. In the present study, a cytometric analysis of T- and B-cell subsets in PLNs was performed during an acute allogeneic GVHR, for comparison purposes. Such a reaction results in a massive node enlargement five to ten times that seen after stimulation with conventional antigens. Acute GVHR is believed to be a direct consequence of the high frequency of alloreactive donor T-cells inducing a massive proliferation of B-cells, almost exclusively of host origin, in GVHR nodes. It is now widely accepted that donor T-cells activated as the result of exposure to foreign MHC antigens in the recipient, secrete various cytokines which assist the host B-cells and bypass the normal B-T cell cooperation. Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model, requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2 incompatible F1 mouse hybrids. 136 74

Incompatibility of human minor histocompatibility (hmH) antigens induces rejection of grafts in organ transplantation and graft versus host disease in bone marrow transplantation if donor and recipient are matched for human leukocyte antigen (HLA) genes. These antigens are recognized only by T cells. We describe here the isolation of hmH peptides recognized by a hmH antigen specific, HLA-B35 restricted CTL clone which was derived from a patient who rejected the kidneys from two HLA-identical sisters. Naturally occurring hmH peptides were isolated from a donor derived B cell line and an HLA-B35 transfected human B cell line by acid elution. Analysis of various HLA class I transfectant cells demonstrated that MHC class I molecules themselves determine the peptides which are naturally processed and presented to T cells.
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PMID:Isolation of human minor histocompatibility peptides. 162

The skin is a major target organ in human graft-versus-host disease (GVHD) after bone-marrow transplantation. GVHD can be induced in mice by i.v. injection of T cells into unirradiated semi-allogeneic or lethally irradiated allogeneic recipients. However, in the murine systemic GVHD model, cutaneous lesions occur only in lethally irradiated recipients. Since lethal irradiation itself might induce the epidermal cell damage, several investigators have employed another murine model of cutaneous GVHD, in which cutaneous lesions were induced by intradermal injection of alloreactive T cell clones. Using this system, it has been reported that both MHC class I- and II-reactive T cell clones can induce cutaneous GVHD in non-irradiated or sublethally irradiated recipients. However, it has remained unknown whether or not freshly prepared T cells are able to induce cutaneous GVHD after local injection into non-irradiated recipients. We show that unprimed T cells can induce cutaneous GVHD after local injection into unirradiated MHC class II- or I + II-disparate recipients. In contrast to alloreactive T cell clones, unprimed T cells could elicit only mild cutaneous lesions in MHC class I-disparate recipients. Since sublethal irradiation of MHC class I-disparate recipients did not result in the manifestation of cutaneous lesions after injection of unprimed T cells, host anti-donor responses by radiosensitive cells could not be responsible for this phenomenon. This experimental system provides a useful model for analysis of the regulation mechanisms in the induction of GVHD by unprimed T cells.
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PMID:Induction of cutaneous graft-versus-host disease by local injection of unprimed T cells. 202 60

The expression of MHC class I and subgroups of class II antigens by keratinocytes and enterocytes has been investigated in patients receiving autologous and allogeneic bone marrow transplants. Allogeneic recipients with graft-versus-host disease (GVHD) expressed all the class II antigens HLA DR, DP and DQ more frequently than pretransplant patients, autologous or allogeneic recipients without GVHD post-BMT (p less than 0.01). Staining for DP and DQ was never detected without DR being present. Whenever there was a lymphocytic infiltrate in the epidermis or single cell necrosis in the gut, DR was expressed on the epithelium. There was no difference in class I expression in GVHD. This study further increases the immunopathological characterization of acute GVHD which may improve the understanding of its pathogenesis.
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PMID:Expression of MHC class I and II antigens by keratinocytes and enterocytes in acute graft-versus-host disease. Newcastle Bone Marrow Transplant Group. 265 8

To explore the relationship between aberrant MHC antigen expression and tissue injury in acute graft-versus-host disease, we performed a sequential histological and immunohistochemical analysis of multiple tissues in acute GVHD generated across complete MHC and multiple minor H incompatibilities in the rat. Two patterns of MHC antigenic modulation were recognized. Aberrant MHC class I and class II antigen expression occurred simultaneously on the epithelial cells of nonlymphoid target tissues early in acute GVHD. This coincided with a lymphoproliferative phase that preceded nonlymphoid tissue injury. The extent of epithelial class II antigen induction predicted the extent of subsequent histological injury. Changes in MHC class II antigen expression were also seen on nonepithelial cells. Interstitial dendritic cells (IDCs) expressing recipient MHC class II antigens increased in both target and nontarget tissues during early GVHD. Recipient class II antigens were also induced on large numbers of microglialike cells in the brain and Kupffer cells in the liver. However, tissue injury did not follow MHC class II antigen induction on nonepithelial cells. These findings are consistent with a role for aberrant epithelial MHC antigen expression in nonlymphoid tissue injury in acute GVHD.
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PMID:Evidence that nonlymphoid tissue injury in acute graft-versus-host disease is limited to epithelial cells aberrantly expressing MHC antigens. 279 19

Irradiated mice (750 rad) were injected with T-depleted bone marrow cells (BMC) and T lymphocytes in various combinations of T/host incompatibility. The epidermis was examined histologically and the incidence of two basic epidermal lesions of graft-vs-host disease (GVHD), the epidermal cell necrosis (ECN) and the lichenoid hyperplastic reaction (LR), were evaluated by a semi-quantitative evaluation. During the acute phase of GVH reaction (GVHR) (days 15 to 25), there was an obvious increase in ECN in reactions elicited by minor loci, whole major histocompatability complex (MHC) differences, or a MHC class I or II difference only. Allogeneic effect without T lymphocyte/epidermis incompatibility did not induce a significant incidence of ECN. Neither depletion of the Ly-2+ nor that of the L3T4+ T lymphocyte subset by treatment with monoclonal antibody (performed in vitro, before injection or also by treatment of the recipient) did prevent the occurrence of ECN, indicating that both T lymphocyte subsets are capable of initiating the epidermal cell damage. The LR was due mainly to the T lymphocytes of the L3T4+, Ly-2- helper phenotype. During chronic GVHR (after 35 days) elicited by either Ly-2+ or L3T4+ lymphocytes, ECN and LR were no longer evident, but the number of epidermal cells and especially the number of replicating cells among the epidermal cells were markedly reduced.
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PMID:Epidermal lesions of the GVHR: evaluation of the role of different MHC and non MHC loci and of the Ly-2+ and L3T4+ T lymphocytes. 295 41

Transfusion with antibody-coated allogeneic blood cells suppresses the cytotoxic antidonor antibody response in a strongly incompatible rat combination (BN----LEW). Cell coating with homologous recipient antidonor antiserum, rat monoclonal antibodies against MHC class I donor antigens, or rabbit antirat lymphocyte serum all were effective. The suppression was not abrogated by repeated booster transfusions with untreated donor blood. Moreover, the suppression extended to antibody-uncoated antigens present on the same donor cell. Not only the antibody response but also the Graft-versus-host reaction against donor antigens was suppressed. The serum of pretreated animals contained suppressive activity. It suppressed the cytotoxic antibody response as well as the cellular immune response (GVH) when transferred into syngeneic recipients. A weaker suppression of antibody response was obtained by transferring spleen cells of pretreated animals into syngeneic recipients. The transfer data suggest that broadly reactive serum factor(s) were mainly responsible for the suppressive effect. Transfusion with LEW-anti-BN-coated donor cells before transplantation induced markedly prolonged kidney graft survival in the BN----LEW combination without additional immunosuppression (untreated controls: 8.4 +/- 0.4, pretreated recipients: 124 +/- 36 days, P less than 10(-4)).
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PMID:Induction of a suppressive serum factor, prevention of sensitization, and prolongation of kidney graft survival in rats by transfusion with antibody-coated blood cells. 306 Oct 74

Injection of parental strain rat lymphocytes under the kidney capsule of semi-allogeneic F1 recipients causes a local graft-versus-host reaction (GVHR) characterized by a heavy mononuclear cell infiltrate and renal tubular destruction. Since the cellular events involved may have relevance to allogeneic tissue damage in GVH disease and allograft rejection, a detailed analysis of the rat renal GVH reaction was performed. A purified CD4+ lymphocyte subpopulation was as effective in mediating a local GVHR as unfractionated parental lymphocytes, but neither naive CD8+ nor specifically sensitized CD8+ lymphocytes produced a detectable renal GVHR. Mononuclear cells harvested from renal GVHR lesions induced by CD4+ lymphocytes were able to lyse natural killer (NK)-sensitive targets when tested in vitro, but showed no allospecific cell-mediated cytotoxicity. Experiments using recombinant PVG rats demonstrated that the ability of the injected cells to cause a GVHR was dependent upon a disparity in MHC class II antigens and that an isolated disparity of MHC class I antigens alone was not a sufficient stimulus to provoke a response. The use of chimaeric rats demonstrated that F1 MHC alloantigens present on kidney parenchyma (but absent on bone marrow-derived cells) were not sufficient to stimulate injected parental lymphocytes, even in the presence of markedly increased amounts of MHC antigens on vascular endothelium and renal tubular cells following in vivo administration of interferon-gamma (IFN-gamma). These results suggest that the renal GVHR in the rat is mediated principally by the interaction of parental CD4+ lymphocytes recognizing and responding to class II F1 alloantigens on bone marrow-derived cells. The resulting tissue damage is most likely a result of a delayed-type hypersensitivity (DTH) phenomenon.
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PMID:The cellular basis of the local graft-versus-host reaction in rat kidney. 326 45

The 402AX teratocarcinoma is a 129/J-derived mouse major histocompatibility complex (MHC) antigen negative tumor that is induced to express H-2b class I antigens during rejection. Resistance to 402AX by MHC allogeneic and syngeneic mice is immunologically mediated and involves the recognition of tumor-associated antigens (TAA) in the context of induced MHC class I antigens. The current studies were undertaken to define the 402AX TAAs. Reconstitution of irradiated susceptible hosts (129/J) with 402AX-primed resistant spleen cells (C57BL/6) results in acute graft-versus-host disease, suggesting that tumor-primed C57BL/6 splenocytes are reactive to tumor genotype (129/J) minor histocompatibility (Hm) antigens. C57BL/6 anti-129/J effector cells, although not directly cytotoxic for 402AX cells, are specifically cold target inhibited by 402AX cells. Genetically susceptible hosts (C3H.SW) immunized to 129/J Hm antigens by skin grafting become resistant to an i.p. challenge of 402AX cells. These results suggest that 129/J Hm antigens may be the TAAs recognized during genetically controlled rejection of the 402AX teratocarcinoma.
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PMID:Resistance to 402AX teratocarcinoma involves immunity to minor histocompatibility antigens. 330 46

Minor histocompatibility (H) antigens are T cell recognized self proteins which can cause graft versus host disease or organ transplant rejection. We have analysed the number of peptide epitopes involved in cytotoxic T lymphocyte (CTL) responses to single or multiple minor H antigens. Bulk CTL responses were generated in H-2b mice differing in one (H-1), two (H-1 and H-25), or multiple (> 29) minor H loci, and HPLC separation was used to analyse the complexity of CTL recognized peptides. Anti-H-1 CTL recognize one out of 50 HPLC peptide fractions and recognition is H-2Kb restricted. The same peptide fraction is also recognized by anti-H-1/H-25 CTL and no additional epitopes are detected, indicating that the H-25 locus does not stimulate CTL when combined with H-1. CTL generated to multiple minor H loci (including H-1 and H-25) recognize two HPLC peptide fractions which are presented by H-2Db and H-2Kb class I molecules, respectively. The H-2Kb presented fraction is the same as that recognized by anti-H-1 and anti-H-1/H-25 CTL, and it is shown to contain a H-1-derived peptide. Subfractionation of the CTL recognized HPLC fractions is consistent with the presence of only one peptide epitope. Thus, in the responses analysed here one minor H locus encodes probably only one CTL epitope. The study provides a molecular explanation for immunodominance among minor H antigens, suggesting that dominant loci encode single peptide epitopes which are presented efficiently by MHC class I molecules enabling them to readily stimulate CTL responses.
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PMID:Few peptides dominate cytotoxic T lymphocyte responses to single and multiple minor histocompatibility antigens. 769 38


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