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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 graft-versus-host reaction (GVHR) in both mice and humans can lead to the development of a broad spectrum of clinical and pathological symptoms. These symptoms are strikingly similar to those of a number of diseases of proven or presumed immunological origin, such as systemic lupus erythematosus (SLE), other collagen vascular diseases, lymphoproliferative disease, and aplastic anemia. The purpose of our investigation was to describe the immunological and pathological events that take place in the course of graft-versus-host disease (GVHD) and to gain insight into the cellular mechanisms underlying these events. To this end, a model was employed in which nonirradiated F1 mice were used as recipients of parental lymphoid cells. By pathological manifestations, 2 basic forms of GVHD can be distinguished in such non-irradiated F1 recipients: One is acute GVHD which is often lethal. It is characterized by a variety of suppressive (hypoplastic) pathological symptoms, including a severe hypoplasia of the lymphohemopoietic system accompanied by aplastic anemia and hypogammaglobulinemia. The other basic form is characterized by stimulatory symptoms, such as persistent lymphoid hyperplasia, formation of autoantibodies, and development of pathological symptoms reminiscent of SLE and other collagen vascular diseases. The suppressive pathological graft-versus-host (GVH) symptoms are caused by T suppressor/killer (TS/K) cells of the donor which react towards allogeneic class-I-structures of the F1 recipient's major histocompatibility complex (MHC). The stimulatory pathological GVH symptoms, by contrast, are caused by donor T helper (TH) cells which react toward the recipient's allogeneic class-II-MHC structures. The possible implications of these observations for the pathogenesis of a number of GVH-like diseases in humans are discussed. The hypothesis is advanced that some of these GVH-like conditions, which arise either e causa ignota or after exposure to certain viruses or drugs, are caused by T lymphocytes reacting against self-MHC structures on lymphohemopoietic cells that were rendered "foreign". By analogy to GVHD, it is conceivable that the development of either stimulatory or suppressive GVH-like symptoms in individuals exposed to a given virus or sensitizing drug depends not on the etiologic agent per se, but on whether the predominant response is made by the individual's TH or TS@K cells. This, in turn, might depend on whether the agent becomes immunogenic in combination with class-II or class-I alloantigens.
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PMID:Pathogenesis of graft-versus-host reactions (GVHR) and GVH-like diseases. 315 4

In order to study the posttransplant evolution of serum immunoglobulin levels, we measured serum IgG, IgA and IgM levels in 50 recipients of allogeneic bone marrow before transplantation and at different intervals thereafter (days 39, 120, 365 and 730). IgG and IgM levels were depressed for 1 year and IgA levels for 2 years posttransplant. Immunoglobulin deficiency was more severe and prolonged in patients with graft versus-host-disease. Hypogammaglobulinemia may contribute to the frequent infections observed in these patients, especially those with chronic graft-versus-host disease.
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PMID:Serum immunoglobulin levels following allogeneic bone marrow transplantation. 389 51

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

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

The exact pathogenic mechanism involved in lichen planus (LP) remains obscure. Two patients who have severe immunodeficiency diseases and who developed LP during the course of their illness are reported here. Both patients had hypogammaglobulinemia and disturbed immune function prior to the development of LP. Although such an association could be coincidental, the development of LP may be related to the underlying immune disturbances. Association of LP with several other disorders of the immune system has been previously observed. Other evidence for the possible involvement of an immunopathogenic mechanism in LP includes (1) deposition of immunoglobulin within the colloid bodies and at the dermoepidermal junction, (2) predominantly T cell dermal infiltrate in LP lesions, and (3) existence of clinical and histologic similarities between graft-versus-host disease and LP.
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PMID:Lichen planus in two immunodeficient hosts. 698 Feb 33

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.
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PMID:The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease. 763 39

Murine graft versus host (GVH) disease takes two forms depending on the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We now report that this marked disparity in disease expression results from a radio-sensitive host mechanism which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing chronic GVH disease. Cellular analysis revealed that protection in chronic GVH disease is mediated by a phenotypically complex system of genetically unrestricted radiosensitive T cells of F1 origin. These cells fail to functionally emerge in mice undergoing acute lethal GVH disease.
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PMID:The host response in graft versus host disease. I. Radiosensitive T cells of host origin inhibit parental anti-F1 cytotoxicity in murine chronic graft versus host disease. 840 29

Intravenous immune globulin (IVIG) has been used with success to prevent and treat infection in patients with immunodeficiencies of humoral immune function. More recently, IVIG has been shown to modulate immune responses and to treat successfully several autoimmune disease. Initial trials in bone marrow transplant recipients were aimed at the prevention of cytomegalovirus (CMV) disease. Although most studies showed such a benefit, CMV prophylaxis is now commonly provided by use of CMV-negative blood products or ganciclovir prophylaxis in, respectively, CMV-seronegative and CMV-seropositive patients. Acute and chronic graft-versus-host disease (GVHD) and associated infections remain critical barriers to the wider application of allogeneic blood or marrow transplantation, especially among patients given HLA-disparate grafts. To date, four controlled clinical trials have shown a significant reduction in acute GVHD in patients given IVIG (500-1000 mg/kg) weekly until 90-120 days post-transplant. In addition, bacterial infection in the early transplant period appears reduced. Meta-analysis of controlled trials reporting acute GVHD endpoints in 379 patients found a relative risk of acute GVHD of 0.68 (95% CI, 0.45-1.02) in IVIG recipients compared to untreated controls. Overall mortality reported in 809 patients in these trials showed an odds ratio of mortality of 0.74 (0.55-0.99) in IVIG recipients compared to controls (values < 1.0 suggest that IVIG was effective in preventing the event). More recently it has been shown that in the absence of hypogammaglobulinaemia, IVIG (500 mg/kg) given monthly from day 90 to 360 did not reduce the incidence of chronic GVHD or late complications. Future research is aimed at characterizing the mechanism of action of suppression of acute GVHD with weekly IVIG prophylaxis and the role of IVIG prophylaxis in patients receiving unrelated marrow grafts.
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PMID:Immunomodulation in allogeneic marrow transplantation: use of intravenous immune globulin to suppress acute graft-versus-host disease. 862 43

Murine graft-versus-host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third party alloantigen is seen in acute lethal GVH disease. In contrast to this, in chronic GVH disease there is polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host veto cell which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing CGVH disease. This cell could be induced in vitro or in vivo in CGVH disease. Using an in vitro system, we now demonstrate that a CD4(+), radiation-sensitive, T cell does emerge in acute lethal GVH disease which is capable of down-regulating cytotoxicity. The cell does not appear to be a veto cell in that it attenuates cytotoxicity directed against nonself alloantigen. The function of this cell does not appear to be influenced by minor lymphocyte stimulatory gene products. We further report that, in ALGVH disease, regulation by this cell is not readily apparent due to the emergence of a CD8(+) T cell of parental (B6) origin, which opposes its action.
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PMID:CD8(+), radiosensitive T cells of parental origin, oppose cells capable of down-regulating cytotoxicity in murine acute lethal graft-versus-host disease. 983 96

The approach to infections in blood and marrow transplant (BMT) recipients involves an understanding of clinical infection syndromes and the natural history of individual infections, taken in the context of patterns of immunosuppression after transplantation and mechanisms underlying immune system reconstitution over time. The conditioning regimen used to prepare the host is a major determinant of host tissue injury and may lead to mucositis or diarrhea, facilitating transmucosal origin of bloodstream infections. Infectious risk also differs between autologous and allogeneic grafts as a consequence of ongoing immunosuppression from graft-versus-host disease and its therapy. Post-transplant complications may mimic infectious processes, and multiple infections may occur in one patient at the same time. Thus, the BMT patient with suspected infection should be evaluated in the context of pretransplant exposure history (infectious disease serologies), conditioning regimen, available culture data from nonsterile mucosal surfaces, previous and recent infections, contemporary transplant complications, and the current degree and duration of neutropenia, cellular immunodeficiency, and hypogammaglobulinemia.
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PMID:Infections in recipients of blood and marrow transplantation. 1055 62


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