Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the stimulating capacities of malignant B cells from non-Hodgkin's lymphomas (NHL) to induce an allogeneic response in primary mixed lymphocyte reaction (MLR). T cells purified from a single healthy donor (KS) were used to compare the responses induced by either malignant or hyperplastic cells. Malignant B cells induced strong proliferation of KS cells independently of their level of expression of adhesion molecules. The KS cells after MLR were predominantly CD3+, CD25+, HLA-DR+, Ki67+ and CD45RO+ T cells, and the CD4/CD8 ratio was heterogeneous (from 0.8 to 2.7). To investigate the role of co-stimulatory molecules CD80 and CD86 for the stimulatory capacities of B cells, the expression of both molecules was analyzed before and during the MLR. Most fresh malignant B cells were negative for CD80 and CD86, whereas co-cultured B cells expressed high levels of both molecules. This expression was crucial for T cell proliferation, since monoclonal antibodies directed against CD80 and CD86 completely abrogated the MLR. We also report that KS responding cells at the end of co-culture were able to lyse fresh B cells used as stimulator cells to different extents (from 10 to 51%), and the level of lysis was enhanced after PMA activation of the target cells. Inhibition experiments using CD8 and CD4 mAb showed that effector cells were mainly CD8+. This report is the first to describe the accessory function of human malignant B cells from NHL and their sensitivity to lysis mediated by CD8+ T cells, and suggests new strategies for the development of antitumor immunity in NHL.
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PMID:Malignant B lymphocytes from non-Hodgkin's lymphoma induce allogeneic proliferative and cytotoxic T cell responses in primary mixed lymphocyte cultures: an important role of co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) in stimulation by tumor cells. 856 20

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expressed mainly by activated T cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, regarded as the malignant components of Hodgkin's disease (HD), display high levels of the counter-receptors for these ligands, ie CD30, CD40 and 4-1BB. CD30L and CD40L are known to share some biological activities that can be linked to the unbalanced secretion of cytokines seen in HD. In addition, cell contact-dependent molecules such as adhesion or activation antigens are critically involved in T cell/H-RS cell interactions. Primary and cultured H-RS cells frequently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD40L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells on the mRNA and protein level, as a result of transcriptional gene activation. Furthermore, enhanced CD54 surface expression by these cells is accompanied by increased shedding of surface-bound CD54, as evidenced by high levels of the 82 kDa soluble (s) CD54 form detectable in culture supernatants after specific stimulation. Addition of CD30L in combination with CD40L to cultured H-RS cells additively enhanced CD54 surface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.
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PMID:The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. 865 79

Hodgkin's disease (HD) is characterized by the presence of the typical, clonal malignant Hodgkin and Reed-Sternberg (H-RS) cells in a hyperplastic background of normal reactive lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils and stromal cells. The neoplastic nature of HD is based on aggressive clinical progression, presence of the proliferating and atypical H-RS cells, aneuploidy and cellular clonality. Immunophenotypical studies have demonstrated frequent expression of lymphoid "activation markers' including CD15, CD25, CD30, CD40, CD54, CD70, CD71, CD80, CD86 and MHC class II and less frequent expression of T- or B-cell-associated antigens by the neoplastic H-RS cells. The clonality of H-RS cells is demonstrated by clonal EBV integration, clonal cytogenetic abnormalities including p53 mutations and clonal immunoglobulin rearrangements in some HD cases. There is involvement of diverse molecules with oncogenic potential, including presence of viruses (Epstein-Barr virus and human herpes virus-6) and/or oncogenes/tumour suppressor genes (bcl-2/bcl-x, p53/MDM-2, c-myc, c-fms, N-ras, lck). The histopathological presentation and characteristic clinical features of HD correlate with an unbalanced production of multiple cytokines and define HD as a tumour of cytokine-producing cells. The proportion of malignant H-RS cells to reactive cellular components and fibrosis is dependent on the production of particular cytokines and allows subtyping of HD cases. The combined use of immunohistochemical, biochemical and molecular techniques has thus allowed recognition that HD represents more than one clinico-pathological entity with different types of H-RS cells. The defined mechanism for the biological nature, origin and oncogenesis of H-RS cells remains not fully understood, but is susceptible to further analysis using modern technology.
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PMID:Pathophysiology of Hodgkin's disease: functional and molecular aspects. 892 38

Hodgkin's disease is characterized by an immune response in the involved tissues that is predominantly CD4 mediated. The CD4+ T-cells are CD45RO+ and CD45RBdim, they express several activation markers but lack CD26, and in vitro can be stimulated to produce gamma-interferon and IL-4, but not IL-2. This is not the usual immunophenotype and cytokine production pattern of Th1, Th2 or Th0 cells and may be a reflection of anergy. The cause of such an anergic reaction is not clear since RS cells express HLA class II as well as the co-stimulator molecules CD80 and CD86. It is possible that a (hypothetical) super antigen expressed on the RS cells may play a role. The absence of IL-2 production however explains the absence of a CD8 mediated response. In addition to that, RS cells generally do not express HLA class I, which allows them to escape CD8 mediated responses. The link between the ineffective immune response in the tissue and the generalized immune deficiency in Hodgkin's disease may consist of several components. These include the influx of mature T-cells into the affected tissues, the secretion of inhibitory molecules by the neoplastic cells and the spill-over of the anergic T-cell response into the general circulation by either the Hodgkin related antigen or also as a result of an IL-4 dominated response. The latter possibility may also be related to the hyper-gamma-globulinaemia and the frequently observed high IgE levels.
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PMID:Immunology of Hodgkin's disease. 892 39

Ligation of CD28 on T cells with its natural ligands B7-1 (CD80) or B7-2 (CD86) provides a major costimulatory signal for T cells and is of potential importance for tumor rejection. We previously reported a strong expression of B7-1 on Reed-Sternberg cells and anaplastic large cell lymphoma cells. We report here our findings on B7-2 expression by malignant lymphomas (n = 70). B7-2 was present on the neoplastic cells of anaplastic large cell lymphoma in two of three cases studied, and on a subpopulation of the malignant cells in one out of four cases of follicular lymphoma. B7-2 was not expressed by the neoplastic cells of the other non-Hodgkin's lymphomas (n = 32), including T cell-rich B cell lymphoma. In contrast, Reed-Sternberg cells in lymph nodes affected by Hodgkin's disease are strongly positive for B7-2 (n = 31). Evidence for a functional correlate of this expression was obtained by our findings that the combination of anti-B7-1 and anti-B7-2 monoclonal antibodies was more effective than each separately in blocking allogeneic T cell activation (proliferation and cytokine secretion) by Hodgkin's disease-derived cell lines as stimulators. The possible role of B7-1 and B7-2 expression for the course and symptomatology of Hodgkin's disease is discussed.
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PMID:Expression of B7-2 (CD86) molecules by Reed-Sternberg cells of Hodgkin's disease. 917 39

Hodgkin's cells (HC) are considered to be the malignant cells of Hodgkin's disease (HD), but despite extensive studies, no conclusive evidence has emerged regarding their non-malignant counterpart and the ontogeny of these cells remains controversial. The analysis of a possible dendritic cell (DC) origin of HC has been hampered to date by the lack of a DC lineage specific marker. The expression of the two DC-associated antigens CD83 and CMRF-44, the B lymphocyte restricted molecule CD79, and the costimulator molecule CD86, was examined in lymph nodes from 23 HD patients using immunohistological techniques. The majority of HC expressed the CD83 (22/23) and CD86 antigens (20/23), whereas expression of the CMRF-44 antigen was variable (10/23) and usually only a subpopulation of HC stained. In contrast, the CD79 antigen was absent from most HC (17/23). The presence of the CD83 antigen on HC in the absence of the CD79 antigen supports a possible DC lineage origin for some HC. Regardless of its role in lineage assignment, CD83 may become a useful immunohistological marker for HD as the CD83 antigen was present on most HC.
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PMID:Hodgkin's cells express CD83, a dendritic cell lineage associated antigen. 1240 53

The CTLA4 receptor is a CD28 homologue which induces inhibitory effect on activated T-cells. Peripheral T-cells proliferate spontaneously in CTLA4-deficient mice. These results led to an analysis of CTLA4 expression in human lymphomas (n = 82) including Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs), using immunohistochemistry. CTLA4 was present in neoplastic cells from most (10/11) T-cell malignancies, except for anaplastic and lymphoblastic subtypes (0/4). Malignant B-cells from rare (3/55) B-NHLs (all of follicular subtype) were also CTLA4-positive. Other B-NHLs (52/55) were negative in malignant B-cells and occasionally positive in T-cells. Reactive small lymphocytes, but not Reed-Sternberg cells, from all (12/12) HD cases were strongly CTLA4-positive. The CTLA4 ligands CD80 and CD86 were simultaneously expressed in most CTLA4-negative lymphoma cases. CTLA4 is thus expressed either in the reactive or in the malignant cell populations, depending on the lymphoma subtype. These results provide new insights leading towards therapeutic strategies based either on enhancement of anti-tumour immunity by CTLA4 blockade in reactive lymphocytes or on triggering of a CTLA4-mediated inhibitory pathway in lymphoma cells.
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PMID:In vivo expression of the CTLA4 inhibitory receptor in malignant and reactive cells from human lymphomas. 939 31

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a molecule expressed on in vitro activated T cells. CTLA-4 shares important sequence homology with CD28 and binds to the same ligands, CD80 (B7-1) and CD86 (B7-2). CTLA-4 probably functions as a negative regulator of T lymphocyte activation in the mouse, although this remains to be proven for human T lymphocytes. We have developed new monoclonal antibodies against human CTLA-4 and have investigated the in situ expression of CTLA-4 in a wide variety of normal and pathological human tissues expressing CD80 and CD86. As revealed in this study, CTLA-4 is expressed on thymocytes in thymic medulla, on a subset of CD4+ T lymphocytes in germinal centers of follicular hyperplasia, on T cells, mainly CD8+, infiltrating skin affected by graft-versus-host disease, and on T cells, mainly CD4+, infiltrating Hodgkin's disease lesions. In immunoelectron microscopy, CTLA-4 was found on the plasma membrane as well as in the hyaloplasm and cytoplasmic vesicles, in agreement with its pattern of expression on in vitro activated T cells. Interestingly, no or at most scarce expression of CTLA-4 was found in granulomatous lymph nodes, T-cell-mediated inflammatory diseases, or non-Hodgkin's lymphomas, regardless of their expression of CD80 or CD86. Thus, expression of CTLA-4 appears to be induced in selective pathological conditions in vivo. The pathways leading to selective induction of CTLA-4 and its role in the pathophysiology of these conditions need to be further investigated.
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PMID:Human CTLA-4 is expressed in situ on T lymphocytes in germinal centers, in cutaneous graft-versus-host disease, and in Hodgkin's disease. 954 57

To elucidate the relationship between Reed-Sternberg (R-S) cells and background T cells, the expression of CD80 and CD86 of R-S cells in Hodgkin's disease (HD), and the ligand CD28 expression and the MIB-1 index of background T cells were immunohistochemically investigated. CD80 and CD86 were found to be expressed on R-S cells in almost all cases of HD. CD28 was expressed with strong intensity on many background T cells around R-S cells. The MIB-1 index of background T cells was 30.3% (range, 15.5-38.9%) and was much higher than 10.9% (range, 9.8-11.7%) in B cell lymphomas. These results suggest that the interaction between CD80 and CD86 on R-S cells, and CD28 on background T cells may induce T cell proliferation and be associated with tumor mass of HD.
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PMID:Costimulatory molecules (CD80 and CD86) on Reed-Sternberg cells are associated with the proliferation of background T cells in Hodgkin's disease. 958 58

Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II-associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease-derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II alphabeta dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II-restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.
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PMID:Deficient major histocompatibility complex class II antigen presentation in a subset of Hodgkin's disease tumor cells. 974 62


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