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Biomedical subjects

D Emilie

Publications and source records attributed to D Emilie.

At least 19 recordsLinked to original sources
PubMed1992

Antagonistic effect of interferon-gamma on tat-induced transactivation of HIV long terminal repeat.

Interferon-gamma (IFN-gamma) has been shown to inhibit human immunodeficiency virus (HIV) replication in macrophages. However, the site of its effect on the HIV infectious cycle is unknown. We show here that IFN-gamma inhibits the transactivation of HIV long terminal repeat (LTR) during viral infection and that it antagonizes tat effect in HT4LacZ-1 cells. HT4LacZ-1 is an indicator CD4+ HeLa cell line for HIV infectivity, because it harbors a HIV LTR-LacZ gene susceptible to transactivation by tat. It was used in combination with a computer-assisted image analyzer to quantify: (i) the number of transactivated foci following HIV infection, (ii) their individual level of transactivation, and (iii) the fusion potency of infected cells. IFN-gamma induced a 75% decrease of the number of transactivated foci following infection of HT4LacZ-1 cells by HIV. The remaining 25% foci still susceptible to transactivation were transactivated at a lower level than in control cultures, and the fusion potency of infected cells was strongly decreased. IFN-gamma acted after HIV entry into the cell and independently of reverse transcription. IFN-gamma antagonized tat-induced LTR transactivation: it inhibited transactivation of HT4LacZ-1 cells when tat was provided either from a SV40-based expression vector of tat or by polyethylene glycol-induced cell fusion with HeLa-tat-III cells. These results suggest that IFN-gamma affects the expression or the activity of cellular factors interacting with tat and that the high level of IFN-gamma production associated with HIV infection plays a role in the establishment of HIV latency.

Genes, tat↗
PubMed1992

Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients.

The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large-cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease.

Interleukin 5 (IL-5), the major factor involved in eosinophil differentiation, is produced by T cells or mast cells. In the present study, we found that eosinophils infiltrating the mucosa of four patients with active coeliac disease also express the IL-5 mRNA. No positive signal was obtained in normal duodenum tissues and in the cell infiltrate from patients submitted to gluten restriction. The identification of labeled mucosal cells as eosinophils relied on their typical morphology. Moreover, highly purified blood eosinophils from three out of four patients with eosinophilia were also strongly labeled with the IL-5 antisense but not with the corresponding sense probe. Together, these results suggest that eosinophils have the capacity to synthesize IL-5, which could contribute to paracrine interactions with T and B cells and, in autocrine fashion, locally participate, through binding to the IL-5 receptor, to eosinophil differentiation and activation. These data might have implications not only in the pathology of coeliac disease but also in other diseases associated with eosinophil infiltration.

Celiac Disease↗
PubMed1992

In vivo production of interleukin-10 by malignant cells in AIDS lymphomas.

Expression of the interleukin (IL)-10/BCRF1 gene was studied by in situ hybridization in tissue samples from acquired immunodeficiency syndrome (AIDS) lymphomas using a BCRF1 probe which also recognizes the human IL-10 sequence. Hybridization was detected in 8 out of 15 lymphomas. In contrast, the IL-10/BCRF1 gene expression was detected in only 1 out of 11 lymphomas from human immunodeficiency virus (HIV)-seronegative patients (p = 0.05). In AIDS lymphomas, the number of cells labeled with a BCRF1-specific probe was dramatically lower than that of cells labeled with the IL-10/BCRF1 probe. Thus, the IL-10 rather than the BCRF1 gene was expressed. Production of IL-10 was associated with that of IL-10 mRNA, as shown by immunodetection of the protein in numerous cells. In contrast, BCRF1-producing cells were rarely detected. Both in situ hybridization and immunochemical experiments indicated that malignant cells were involved in this IL-10 synthesis. IL-10 production in AIDS lymphomas was associated with the presence of Epstein-Barr virus (EBV) in lymphomatous cells (p = 0.02). As IL-10 is a potent growth factor for human B lymphocytes, these results suggest that IL-10 may stimulate the proliferation of malignant cells in an autocrine pathway in a number of AIDS lymphomas, and that EBV and HIV may synergistically trigger its production.

Gene Expression↗
PubMed1992

Production of cytokines in sarcoid lymph nodes: preferential expression of interleukin-1 beta and interferon-gamma genes.

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-2, and interferon-gamma (IFN-gamma) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1 beta gene was preferentially expressed. The distribution of cells containing IL-1 beta mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-alpha gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1 alpha gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1 beta gene was significantly higher than that of cells expressing TNF-alpha gene (P = .001), IL-6 gene (P = .007), or IL-1 alpha gene (P less than .001). Of the cells expressing lymphokine genes, those expressing the IFN-gamma gene were 31.9 (+/- 7.6) times more frequent than those expressing the IL-2 gene (P less than .001). Cells containing IFN-gamma mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1 beta gene and the IFN-gamma gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.

Cytokines↗
PubMed1992

Monokine gene expression in normal human liver: selective involvement of the portal compartment.

Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL-1 beta and of IL-6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL-1 beta mRNA or IL-6 mRNA in all cases. Cells expressing either the IL-1 beta gene or the IL-6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL-1 beta gene and of the IL-6 gene may be induced by gut-derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.

Gene Expression↗
PubMed1992

Activation of macrophages and cytotoxic cells during cytomegalovirus pneumonia complicating lung transplantations.

The functional status of immune cells within human transplanted lungs was analyzed during cytomegalovirus (CMV) pneumonia complicating lung and heart-lung transplantations. The expression of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) genes is a marker for the activation of macrophages as is that of serine esterase B (SE-B) gene for cytotoxic cells. The levels of expression of these genes by bronchoalveolar lavage (BAL) cells were determined by in situ hybridization. Eight cases of CMV pneumonia were included in this study. BAL cells from either rejection episodes (eight cases) or control transplanted patients experiencing neither infection nor allograft rejection (eight cases) were analyzed in parallel. In the control patients, virtually no cells expressed the IL-1 beta, the IL-6, or the SE-B genes. In contrast, these three genes were all expressed in samples from patients with CMV pneumonia. IL-1 beta gene-expressing cells were abundant in all infected patients (mean +/- SEM: 898 +/- 449 positive cells per 10(4) cells, p less than 0.001, compared with those in control patients). IL-6 gene-expressing cells were less numerous (92 +/- 74 positive cells per 10(4) cells) and present in five of the eight cases of CMV pneumonia. Activated cytotoxic cells were detected in seven of the eight cases of CMV pneumonia (36.5 +/- 19 SE-B gene-expressing cells per 10(4) cells, p less than 0.001). During allograft rejections (eight cases) IL-1 beta gene-expressing cells were present in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Interleukin-6 gene expression in Castleman's disease.

Defined by histological criteria, Castleman's disease (CD) is a clinically and histologically heterogeneous syndrome. The functional status of immune cells in affected tissues may vary between the different forms of the disease. To address this question, the expression of cytokine genes in eight CD lymph nodes was analyzed by in situ hybridization. Two lymph nodes were taken from patients with a localized form of the disease associated with systemic manifestations, two from patients with a localized form without systemic symptoms, and four from patients with a multicentric form. Five lymph nodes exhibiting a benign follicular hyperplasia were used as controls. The interleukin-6 (IL-6) gene was expressed at a very high level in two cases: the two localized forms of CD associated with systemic manifestations. IL-6 gene overexpression occurred inside follicles of these lymph nodes. The morphology of follicular cells hybridizing with the IL-6 probe or labeled with an anti-IL-6 monoclonal antibody suggested that follicular dendritic cells expressed the IL-6 gene. In contrast, no IL-6 gene expression was detected inside follicles of the six other CD lymph nodes or of the five control lymph nodes. In interfollicular areas, IL-6 gene-expressing cells were detected in all lymph nodes by both in situ hybridization and immunohistochemistry. In CD lymph nodes, positive cells were located outside sinuses, in close contact with blood vessels and plasma cells. This distribution was clearly different from that observed in control lymph nodes, in which IL-6 gene-expressing cells were present inside sinuses. A similar difference between CD and control lymph nodes was observed for the distribution of IL-1 beta and IL-1 alpha gene-expressing cells in interfollicular areas. The morphology of interfollicular IL-6-producing cells was heterogeneous, consistent with that of macrophages, interdigitating cells, lymphocytes, and endothelial cells, and different from that of plasma cells. Taken together these results show that CD is consistently associated with a particular pattern of IL-6 gene expression in interfollicular areas whereas elevated IL-6 gene expression inside follicles only occurs in the localized form of the disease associated with systemic manifestations. The variable pattern of IL-6 gene expression as well as the clinical and histologic heterogeneity of CD indicate that different immune mechanisms may be involved in the different forms of this disease.

Adolescent↗
PubMed1991

In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients.

We analyzed by in situ hybridization the expression of four interleukin genes (interleukin-beta [IL-1 beta], IL-6, IL-2, and interferon-gamma) in seven thymuses displaying a follicular hyperplasia. The seven thymuses were obtained from patients with myasthenia gravis. Interleukin-1 beta- and IL-6-producing cells were detected in similar amounts and with similar distributions: mainly in perifollicular areas and in the connective structures emerging from the septae at the site of cortex disruption. The comparison of in situ hybridization and immunohistochemical results suggested that thymic epithelial cells and/or perifollicular macrophages were responsible for this production. Interleukin-2-producing cells were detected in perifollicular areas and, to a lesser extent, inside follicles. They were clearly outnumbered by CD25-positive cells which were similarly distributed. Despite the expression of these molecular and immunohistochemical markers of T-cell activation, interferon-gamma-producing cells were extremely rare in myasthenic thymuses. The pattern of interleukin production (which was virtually absent in normal control thymuses) in myasthenic thymuses was different from that in benign hyperplastic lymph nodes. This interleukin production may play a role in the development of follicular hyperplasia in myasthenic thymuses, a phenomenon which is associated with the in situ production of autoantibodies.

Adolescent↗
PubMed1991

Interleukin-2 and interferon-gamma production in follicular lymphomas.

In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low-grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine-synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T-cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction.

Humans↗
PubMed1991

HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry.

Recent epidemiological and virological data suggest that the incidence of maternofetal transmission of HIV-1 infection is between 20 and 30%. The available evidence points to a possible role of peri- and postnatal contamination, but the isolation of HIV from fetuses shows that transplacental transmission also occurs. We attempted to detect, by means of an immunohistochemical method, HIV proteins in frozen placentas from 75 HIV-1-positive women (30 at term, 45 induced abortions). In addition, in situ hybridization using HIV-specific probes was performed in three cases. Neither HIV proteins nor nucleic acid sequences were detected, but CD4+ mononuclear cells were present in the chorion and villi, regardless of the clinical and biological status of the mother (particularly in the nine cases in which the infants were infected). There are several possible mechanisms involving the placenta in the maternofetal transmission of HIV, including active transport of the HIV-immunoglobulin G complex via Fc receptors on trophoblastic cells, passive transplacental passage of HIV during a viraemic episode, the passage of infected maternal cells, and infection of the placenta itself. The methods we used could not rule out the presence of HIV DNA provirus within the genome of placental cells. In any event, immunohistochemical detection of HIV proteins in the placenta is not a technique suitable for the prenatal diagnosis of HIV infection or for identifying newborns likely to develop HIV infection.

Adult↗
PubMed1991

Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients.

Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non-HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Individual germinal centres of myasthenia gravis human thymuses contain polyclonal activated B cells that express all the Vh and Vk families.

Using in situ hybridization, we analysed the immunoglobulin repertoire expressed by the B cells present in myasthenia gravis thymuses from four patients. B cells, mostly in activated state, were clustered in germinal centres, in which multiple isotypes were identified. A majority of cells expressed IgG as compared with IgM, with a roughly similar contribution of kappa and lambda chains. Hybridization with the six VH and the 4 VK human family probes was observed in serial sections, providing additional evidence that individual germinal centres were polyclonal. The thymic B cell repertoire closely reflected the VH and the VK family usage of normal peripheral blood lymphocytes with the preferential utilization of VH3, VK1 and VK3.

Adult↗