Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of three cellular adhesion molecules, ICAM-1, ELAM-1 and VCAM-1, was studied in normal rectal mucosa and in graft-versus-host disease (GvHD) using immunohistological and morphometric techniques. In normal controls, ICAM-1 was demonstrable on endothelial cells and leucocytes within the lamina propria, ELAM-1 on endothelial cells only and VCAM-1 on lamina propria leucocytes, many of which exhibited long dendritic processes surrounding the glands. In GvHD, the enterocytes became positive for ICAM-1 and this was often associated with the presence of intra-epithelial LFA-1+ lymphocytes and macrophages, the latter containing debris of apoptotic cells. The staining was, however, restricted to the luminal membrane of the epithelial cells, raising doubts about the role of ICAM-1 as a ligand for LFA-1 on mucosal leucocytes in rectal GvHD. ELAM-1 expression was increased in GvHD both in terms of the length of positive endothelium and staining intensity. VACM-1 was increased on endothelial cells but not leucocytes in the lamina propria in contrast to our previous findings in cutaneous GvHD where VCAM-1+ dendritic cells were increased and endothelial cells remained negative. Normal patterns of adhesion molecule staining were seen in two biopsies exhibiting no morphological evidence of GvHD, from patients who had strong clinical evidence of the disease, indicating that immunostaining for these molecules is unlikely to be of help in improving the sensitivity of histological diagnosis. However, the possibility that adhesion molecule staining may be useful in improving diagnostic specificity by helping to distinguish GvHD from identical histological changes produced by irradiation and cytotoxic drugs is worthy of further investigation.
 ...
PMID:Expression of adhesion molecules in human intestinal graft-versus-host disease. 137 Sep 27

Because keratinocytes (KCs) express HLA-DR in a wide variety of skin diseases in which mononuclear leukocytes are observed in close apposition to KCs (i.e., graft-versus-host disease), and since gamma interferon (IFN-gamma) induces HLA-DR expression on KCs, we asked whether IFN-gamma treatment of KCs would influence the adherence of mononuclear leukocytes. When allogeneic peripheral blood mononuclear leukocytes (PBML) and a Leu-3+ T cell clone were coincubated with IFN-gamma-treated KCs (300 U/ml, 3 days), there was a marked increase in binding compared with nontreated KCs. Similar binding results were obtained using a cutaneous squamous carcinoma cell line (SCL-1) after IFN-gamma treatment. The IFN effect was relatively specific for IFN-gamma, as neither IFN-alpha nor -beta had any effect. Tumor necrosis factor exposure (500 U/ml, 3 days) increased the binding of the Leu-3+ T cell clone to both KCs and SCL-1 cells. Neutrophils displayed a less marked (but statistically significant) increase in binding to IFN-gamma-treated KCs. Using the Leu-3+ cell clone and SCL-1 cells, detailed kinetic analysis of the effect of IFN-gamma on binding was performed. The increased adherence between the cells began to appear after only 7 hours of treatment with r-IFN-gamma (300 U/ml) and reached a plateau at 48 hours, with significantly enhanced binding continuing for at least 48 hours after removal of IFN-gamma. The mechanism of binding was explored by preincubation of the PBML/Leu-3+ T cells with anti-LFA-1 (lymphocyte function-associated antigen) antibody (0.6-6.0 micrograms/ml), which totally inhibited the binding with no effect by anti-LFA-2 or -3 or class I or II antibodies despite documented binding of these antibodies to the cells. These results suggest that, after exposure to IFN-gamma, the ability of KCs to bind mononuclear leukocytes is strongly enhanced, and this adherence may be important in leukocyte trafficking in the skin as well as contributing to altered KC-leukocyte interaction, which may be of fundamental importance in a variety of skin disease.
 ...
PMID:Recombinant gamma interferon increases the binding of peripheral blood mononuclear leukocytes and a Leu-3+ T lymphocyte clone to cultured keratinocytes and to a malignant cutaneous squamous carcinoma cell line that is blocked by antibody against the LFA-1 molecule. 244 90

An increasing number of diseases may be treated successfully by allogeneic bone marrow transplantation (BMT). Initially used for the treatment of immunodeficiency where a cell series or product is replaced, it has now become routine treatment for many forms of leukemia where the transplant provides the rescue after lethal marrow ablation. Recently, diseases such as thalassemia and other inherited metabolic diseases have also been treated by BMT. Formerly the problems of BMT were mainly concerned with graft versus host disease (GVHD) in HLA-matched transplants with HLA-mismatched ones not being possible as GVHD was usually fatal. Since the development of techniques for T cell removal the incidence of GVHD has greatly diminished. T cell removal has also allowed HLA haploidentical mismatched grafts to be performed successfully for immunodeficiency, but there is still a high graft rejection rate in leukemia. This also occurs to a lesser extent with HLA-matched grafts in leukemia. Furthermore, in certain forms of leukemia, particularly chronic granulocytic leukemia, the relapse rate after T cell-depleted BMT is much higher. Trials of better forms of bone marrow conditioning of the recipient are being attempted in order to prevent graft rejection and leukemia relapse. These include total lymphoid irradiation, heavier irradiation and chemotherapeutic regimens, or the use of in vivo monoclonal antibodies such as CAMPATH 1G or anti-LFA-1 (CD11a). In the future, positive selection of stem cells combined with hemopoietic growth factors may allow engraftment without graft versus host disease. This should become the method of choice for autologous transplantation for malignancy. Two monoclonal antibodies directed against the human progenitor cell antigen 1 (HPCA-1) (CD34) have been used for autologous positive stem cell selection in primates and these cells gave full hemopoietic reconstitution in the animals following lethal total body irradiation.
 ...
PMID:Recent advances in bone marrow transplantation. 256 39

The mouse monoclonal antibody 25-3 specific for the alpha subunit of LFA-1 (CD11a) has been infused to children undergoing HLA non-identical bone marrow transplantation because of lethal inherited diseases or of leukemia in order to prevent graft failure. We have assessed the serum concentrations of the antibody infused according to two regimens: 0.1 mg/kg five times, every alternate day (eight patients) or 0.2 mg/kg daily for 10 days (30 patients). Serum trough levels of 25-3 antibody in the first group were constantly found to be low (less than 0.6 micrograms/ml) while 25-3 serum concentration in the second group rose progressively to a mean value of 2.2 micrograms/ml. Serum antibody concentrations were significantly lower in patients with greater antigenic mass, i.e. with splenomegaly, or non conditioned. The engraftment rate was slightly higher in patients treated by the daily infusion of 25-3 for 10 days. No immunization against 25-3 antibody occurred. One patient who subsequently received other mouse anti-B cell antibodies eventually produced anti-isotype antibodies. The consequences of 25-3 infusion on leukocyte counts has been evaluated in the group of patients (n = 6) with severe combined immunodeficiency who did not receive any chemotherapy and in one who was treated with 25-3 because of acute graft-versus-host disease. In none of the cases did 25-3 antibody infusion modify blood leukocyte counts. In addition, it was shown that saturation of LFA-1 on leukocytes was a transient phenomenon, since it could not be found 24 h following infusion of 25-3 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In vivo infusion of anti LFA-1 antibody in HLA non-identical bone marrow transplantation in children: serum concentrations and biological effects. 267 57

Sensitive immunofluorescence and immunoperoxidase techniques were used to test an extensive range of monoclonal antibodies for reactivity with Kupffer cells and interstitial dendritic cells (DCs) in cryostat-cut sections of human liver. Leucocytes with a dendritic cell morphology were identified with CD45 (antileucocyte common) reagents in portal tracts, predominantly around bile ducts, and these cells stained strongly for the HLA-DP, DQ, and DR antigens. Kupffer cells stained less intensely with anti-class-II reagents, particularly anti-HLA-DQ. The interstitial DCs expressed the LFA-1 antigen but failed to stain with CD11b, CD11c, and the defined T and B cell CD antibodies; nor did they stain with antibodies to FcR1, FcR11, FcRIII, or the C3b receptor. Of the myeloid monoclonal antibodies available from the 3rd Leucocyte Differentiation Antigen Workshop, only Y2/131, Ki-M7, Ki-M8, and a minority of CD14 antibodies stained DCs, whereas Kupffer cells showed a wider reactivity with antimacrophage antibodies including those of workshop groups 11, 15, 16, and other unique antibodies. A 2nd probable DC population was identified in the liver capsule that had a similar phenotype to portal interstitial DCs. Although some minor phenotypic differences between liver portal DCs and the phenotypes of Langerhans cells and isolated tonsil DCs were noted, our results support the view that there is a unique hemopoietic lineage of DCs. The presence of DCs, which stimulate strong allogeneic T cell responses, in the portal triads is consistent with the fact that the histologic changes of graft-versus-host disease seen in bone marrow transplantation and the lymphocytic infiltrate in a rejecting liver allograft occur predominantly in the periportal region.
 ...
PMID:Characterization of interstitial dendritic cells in human liver. 305 97

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.
 ...
PMID:Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. 759 66

A model for investigating graft-versus-leukemia (GVL) activity following syngeneic and MHC-compatible allogeneic BMT has been developed in C57BL/6 (B6) mice with use of the c-myc retrovirus-transformed MMB3.19 myeloid leukemia line. The MMB3.19 line was derived from a B6 mouse and expresses monocyte/macrophage markers, including Mac-1, Mac-2, F4/80, and LFA-1, in addition to H-2 class I and class II molecules. A challenge dosage of 10(5) of these leukemia cells was found to be completely lethal when injected into irradiated (850 cGy) B6 recipients, 1 day after the transplantation of syngeneic donor T cell-depleted-bone marrow. The addition of T lymphocytes to the donor inoculum prolonged recipient survival, and both CD4+ and CD8+ subsets were found to be capable of mediating this GVL activity. For the MHC-compatible allogeneic model, the C3H.SW-->B6 (850 cGy) strain combination was utilized, in which CD8+ T cells are known to cause graft-versus-host disease directed to minor histocompatibility antigens expressed by the recipient. In this case, both CD(4+)- and CD(8+)-enriched T cells were found to be capable of mediating GVL activity to MMB3.19 challenge, particularly if donor mice were presensitized with leukemia cells. Of most significance, only the donor CD4+ T cells mediated a GVL effect without the apparent induction of graft-versus-host disease.
 ...
PMID:Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation. 791 87

Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed whether IFN gamma-treated cultured human keratinocytes would activate established Th cell clones in vitro. Three allo DR specific T cell clones were induced to proliferate in a HLA-DR and LFA-1/ICAM-1 dependent fashion upon coculture with intact layers of IFN gamma stimulated keratinocytes. Likewise, keratinocytes also could activate two out of four minor histocompatibility (mH) antigen specific Th cell clones obtained from peripheral blood leukocytes (PBL) of graft versus host disease patients. The T cell activating potential of MHC class II+ keratinocytes was shown to be relatively low compared to specialized APC as PMNC and EBV-BLCL. Most strikingly, measurable allo MHC and mH antigen specific Th cell proliferation was only induced by using adherent keratinocytes at low cell densities, but not by keratinocytes in suspension. The results presented here indicate that in vitro conditions may crucially influence observations regarding the T cell activating potential of MHC class II expressing keratinocytes. Furthermore, our results indicate that, in addition to a tolerizing effect as suggested by previous reports, interaction of primed antigen specific T cells with activated keratinocytes may also result in enhancement of a cutaneous immune response in vivo.
 ...
PMID:Human keratinocytes activate primed major and minor histocompatibility antigen specific Th cells in vitro. 791 50

Human cord blood is an attractive alternative to marrow-derived stem cells for transplantation. Experiences with cord blood transplants suggest that graft-versus-host disease (GvHD) may be less readily induced, even in the face of HLA differences. However, this decreased potential for GvHD might also abrogate the graft-versus-leukemia (GvL) effects of the transplant. The GvL potential might be doubly compromised since cord blood NK activity is also decreased. We have compared alloreactivity, NK cell activity and lymphokine-activated killer cell (LAK) activity of cord blood mononuclear cells with adult mononuclear cells. We find a reduced (but not absent) alloproliferative, allostimulatory and allocytotoxic capacity of cord blood mononuclear cells. Phenotyping revealed no significant differences in the proportion of T cells in cord-versus-adult blood, but cord blood T cells were nearly all of the naive CD45RA subset. Expression of LFA-1 alpha and LFA-1 beta was normal on resting cord T cells; however, they expressed significantly less ICAM-1 (CD54) than did adult PBMC. Cord blood B cells and monocytes expressed normal levels of HLA Class II. Although no differences were found in NK cell percentages or subsets in resting cord blood, cord blood NK activity was very low. However, LAK activity was much more readily induced in cord blood as compared to adult PBMC, which could be explained in part by a higher frequency of LAK precursors (LAKp). Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML, and CML.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of cord blood lymphocyte subpopulations. 792 75

Rare cases of graft-versus-host disease after liver transplantation indicate that donor lymphocytes may be transferred to the recipient by human liver grafts. In this study, we have analyzed the number and subpopulations of donor lymphocytes transferred by liver grafts in order to evaluate the potential relevance of these cells after transplantation. Therefore, mononuclear cells were isolated from the tissue of perfused human donor livers and from the associated lymph nodes. The number of lymphocytes, their location, and surface marker expression were determined by immunostaining. The majority of lymphocytes transferred by the grafts were found within the liver tissue (5.3 +/- 2.9 x 10(9) cells). These lymphocytes are mainly T and NK cells, predominantly CD8+, are partially activated (28% HLA-DR+), and show strong adhesion molecule expression (88% LFA-1(3+)). In addition, 20-500 x 10(6) of resting lymphocytes, predominantly T and B cells, are transmitted by lymph nodes. These findings demonstrate that considerable numbers of donor lymphocytes of distinct phenotype are regularly transmitted to the recipient by human liver grafts and may be of functional relevance after transplantation.
 ...
PMID:Passenger lymphocytes in human liver allografts and their potential role after transplantation. 810 72


1 2 3 Next >>