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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)

To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic major histocompatibility complex (MHC) allodeterminants and interact with T-cell receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel of monoclonal antibodies with a two-colour direct immunofluorescence method, we found a significant increase in the expression of the V beta 5.3 subfamily in the HIV-positive patient group compared with controls (p less than 0.01). Selected increase in expression of V beta sequences has been described in various autoimmune conditions and our findings raise the possibility that the immunopathological damage from HIV infection may be due to the induction of autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus could represent an autoimmune process similar to graft-versus-host disease.
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PMID:T-cell receptor variable gene products and early HIV-1 infection. 135 71

Lethal graft-versus-host disease (GVHD) can be induced in MHC-matched strain combinations which differ in their expression of multiple minor histocompatibility (H) antigens. It has been shown that CD8+ T cells play an important role in the development of disease directed to the minor H antigens, and that initial indications were that highly purified preparations of these cells were capable of mediating GVHD, without apparent 'help' from mature donor-derived CD4+ T cells. To further strengthen this hypothesis, the current study was undertaken with the B10.BR----CBA strain combination in which irradiated recipient mice were additionally treated with an anti-CD4 monoclonal antibody, as a single or repeated injection, to minimize the presence of either residual host CD4+ cells or recently generated donor-derived CD4+ cells at later stages of disease development. The results indicate that these treatments do not affect the GVHD outcome and that the CD8+ cells are indeed capable of inducing disease independent of CD4+ 'help'. The addition of donor CD4+ T cells in the inoculum, however, does enhance the potential of these CD8+ cells, and is observed with both low and high dosages of CD4+ cells. CD4+ T cells, on their own, have also been observed to cause GVHD directed to minor H antigens in certain strain combinations, and their response has been further characterized in this study. Results indicate that CD4+ cells capable of mediating GVHD in the B10.D2----DBA/2 strain combination can do so over a wide range of recipient irradiation exposures. The transfer of high dosages of CD4+ cells only shortens survival times of the recipients and does not afford any apparent protection phenomenon as previously observed in CD4+ cell mediated anti-class II MHC GVHD. The study also indicates that neither CD4+ nor CD8+ cells responsible for GVHD directed to minor H antigens seem capable of targeting host stem cell elements.
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PMID:Lethal graft-versus-host disease in mice directed to multiple minor histocompatibility antigens: features of CD8+ and CD4+ T cell responses. 135 63

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus. 135 59

To characterize immune suppressive and hematopoietic features of enriched subsets of human marrow cells, we separated these cells on Percoll density gradients. CD4+ and CD8+ T cells (CD3+) were enriched in the high-density marrow cell fractions and reduced in low-density fractions. CD4-CD8- (CD3+) T cells expressing the alpha beta T-cell antigen receptor were at least 10 times less numerous than the CD4+ and CD8+ T cells in all fractions. Purified populations of the CD4-CD8- alpha beta + T cells obtained by flow cytometry suppressed the mixed leukocyte reaction (MLR). Another population of suppressor cells that expressed neither T-cell (CD3) nor natural killer cell (CD16) surface markers was also identified. The latter cells had the phenotypic and functional characteristics of "natural suppressor" cells. Suppressor cell activity was enriched in the low-density fractions along with hematopoietic progenitors (colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid). The progenitor and suppressor cell activities were depleted in high-density fractions. The latter fractions made vigorous responses in the MLR. The low-density fractions, which accounted for less than 10% of the input marrow cells, suppressed the MLR and did not respond. Further evaluation of the low-density fractions may be of value in allogeneic bone marrow transplantation due to the reduction of CD4+ and CD8+ T cells and the enrichment of hematopoietic progenitors as well as immune suppressor cells that may inhibit graft-versus-host disease.
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PMID:T-cell subsets and suppressor cells in human bone marrow. 146 27

We have studied histological and immunohistological specimens of 39 skin biopsies from 21, and 30 rectal biopsies from 17 bone marrow transplant recipients. The biopsies were taken before transplantation, during acute and chronic graft-versus-host disease (GVHD), and at times with no GVHD. In biopsies taken during cutaneous aGVHD grade I to III, epithelial changes were seen in 16/23 biopsies. The cutaneous infiltrates during aGVHD consisted of CD2-, CD4-, CD8- and FMC-33-positive cells both in the epithelium and in the dermis. CD57-positive NK cells were also detected in most biopsies. During chronic GVHD the cutaneous cellular infiltrates were similar to those seen in moderate aGVHD, i.e. both CD4- and CD8-positive lymphoid cells were present. When the biopsy was taken after the beginning of corticosteroid treatment for aGVHD, or at times when the patient did not have GVHD symptoms, the cellular infiltrates were considerably smaller in the dermis. During clinical intestinal aGVHD mucosal epithelial changes were relatively uncommon; instead, increased numbers of both CD4- and CD8-positive lymphocytes in the lamina propria (LP) were seen in 11/13 samples. During chronic GVHD the number of CD4-positive cells exceeded that of CD8-positive cells in the LP, and the large lymphoid infiltrates also reached the muscularis mucosae. In rectal biopsies the differences were not so prominent because most of the pretransplant biopsies showed CD2-, CD4-, CD8- and CD57-positive lymphocytes both in the lamina propria and epithelium.
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PMID:Immunohistology of skin and rectum biopsies in bone marrow transplant recipients. 149 80

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

We searched for evidence that immunodeficiency in graft-versus-host disease (GVHD) is in part due to alloimmune damage to lymph nodes. We used immunoperoxidase techniques to stain T-cell subsets, pan-B cells, and follicular dendritic reticular cells (FDRC) in frozen sections of lymph nodes from 80 marrow graft recipients (56 with GVHD, 11 autografts, and 13 allografts without GVHD). We found that 46% of the GVHD patients had reversed CD4:CD8 ratios and only 13% of non-GVHD patients had such disturbed ratios (p = 0.006). Pan-B (CD22) cell labeling was present in the follicular regions of 73% of patients without GVHD and only 53% of patients with GVHD (p = 0.05). Focal FDRC staining was geographically concordant with clusters of B cells in 88% of cases (p less than 10(-7)). These data confirm that disturbed intranodal CD4:CD8 ratios are present more frequently in GVHD patients than in non-GVHD patients or in autografted patients. They suggest more delayed follicular B-cell reconstitution in GVHD patients. They show an extremely tight association of FDRC with clusters of B cells in the recovering lymph node, as in the developing fetal node. We hypothesize that the lack of follicular dendritic cells may contribute to dysfunctional B-cell maturation by ablating orderly antigen presentation and clonal expansion in the lymph node cortex.
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PMID:Abnormal CD4:CD8 ratios and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GVHD): an immunohistological study. 150 36

As HIV readily kills CD4 cells in vitro it has been widely assumed that this would account for the declining CD4 counts in vivo. A growing number of reports suggest that the pathogenesis of AIDS is considerably more complex than had been thought. A number of indirect mechanisms for CD4 cell death have been proposed. In this review of alternative theories which could explain the features of AIDS, autoreactivity and genetic restriction to the development of disease are considered the most important. In addition it is suggested that if HIV is able to mimic MHC antigens on the surface of antigen presenting cells then this could stimulate 'allo reactive' T lymphocytes, which would explain the marked similarity of HIV infection to chronic graft versus host disease.
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PMID:The pathogenesis of AIDS: classical and alternative views. 158 22

We investigated the capacity of monoclonal antibody (mAb) treatment to prevent graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice, employing anti-T cell (subset) mAb and a fully allogeneic strain combination. In this strain combination, purified CD4+ cells were able to induce a lethal GVH reaction, whereas purified CD8+ cells were not. In the same strain combination, a single intraperitoneal injection of IgG2b anti-Thy-1 mAb, one day after reconstitution, caused a dose-dependent improvement of the survival. A single injection of a dose as low as 12.5 micrograms per mouse was already effective. Intravenous and intraperitoneal administration of the mAb appeared equally effective. For effective prevention of GVHD the treatment could be postponed until the 4th day after transplantation, but treatment delayed until day 6 was no longer effective. Treatment with IgG2b mAb specific for either helper or cytotoxic T cells also led to improvement of GVHD and survival, but was less effective than treatment with anti-Thy-1 mAb. Clinically, there was a difference in the effectiveness of anti-CD4 and anti-CD8 treatment, since symptoms of GVHD started earlier in the anti-CD8 treated group and the survival was better in the anti-CD4 treated group. These results press for prospective clinical studies employing anti-T cell mAb treatment early after allogeneic bone marrow transplantation, especially in HLA mismatched cases.
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PMID:Prevention of lethal graft-vs.-host disease by a single low dose injection of anti-T cell monoclonal antibody to the allograft recipients. 167 55

We performed an immunohistochemical analysis of skin biopsies from 13 allogeneic bone marrow transplant (BMT) recipients, undergoing either acute graft-versus-host-disease (aGVHD, n = 8) or chronic GVHD (cGVHD, n = 5). A panel of different monoclonal antibodies (MoAb) was employed including anti-CD2, -CD3, -CD4, -CD8, -CD11b, -CD16, -CD56, and -CD57, as well as a recently described reagent (HP-3B1) specific for a novel natural killer (NK)-associated cell-surface antigen (Kp43). Our data indicate that in aGVHD lesions the proportions of CD2+ cells often exceeded those detected with anti-CD3 MoAb. Double labeling confirmed the presence of CD2+ CD3- lymphocytes and suggested the coexpression in some cells of CD2 and CD11b. When MoAb specific for non-lineage-restricted NK-associated markers were employed, anti-CD56 and -CD57 occasionally stained variable numbers of lymphocytes (means = 14.6% of mononuclear cells in 0.05 mm2, range less than 1-48% and means = 10.3%, range 2-25%, respectively), whereas no CD16+ lymphocytes were observed. In contrast, most samples consistently displayed substantial proportions of Kp43+ cells (means = 32.8%, range 12-63%), which appeared CD3- and were mainly located at the dermoepidermal junction. On the other hand, sections from most (four of five) cGVHD lichenoid lesions analyzed displayed lower proportions of Kp43+ and CD56+ cells. Our data point out the interest of the anti-Kp43 MoAb to identify NK cells in aGVHD lesions, suggesting their pathogenetic participation.
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PMID:Identification of natural killer (NK) cells in lesions of human cutaneous graft-versus-host disease: expression of a novel NK-associated surface antigen (Kp43) in mononuclear infiltrates. 168 91


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