Giant cell formation in Hodgkin's diseaseFormation de cellules géantes dans la maladie de Hodgkin

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Summary

The identity of Reed-Sternberg cells in Hodgkin's disease has remained an unresolved issue, though many studies have addressed this question. Giant cells are usually formed either by endomitosis without cytoplasmic division or by cell fusion through cytokines or viruses. Growing evidence associates Epstein-Barr virus (EBV) with Hodgkin's disease, a major issue being whether EBV is a passenger virus or has an aetiological role.

This communication describes experimental conditions enabling observation of giant cell cytogenesis from peripheral blood mononuclear cells in culture. Mononuclear cells were isolated from autologous peripheral blood and cocultured with a single-cell suspension obtained from Hodgkin's lymph nodes in a culture chamber where the two cell populations are isolated by a microporous membrane that allows only cytokines and viruses to pass through. Under these experimental conditions, giant cells are formed in the peripheral blood mononuclear cell fraction; some of them appear morphologically indistinguishable from Reed-Sternberg cells and their mononuclear variant, while others much resemble Langhans giant cells. Some of these giant cells are positive for EBV DNA by in situ hybridization. These results suggest that an EBV-dependent biological activity is responsible for giant cell cytogenesis originating from lymphocytes and monocytes, induced either by EBV and/or cytokines.

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Malgré les nombreuses études menées sur ce sujet, l'identité des cellules de Reed-Sternberg dans la maladie de Hodgkin est une question restée sans réponse.

Les cellules géantes se forment habituellement par endomitose sans division du cytoplasme ou par fusion cellulaire via les cytokines ou les virus. Il apparaît de plus en plus évident que le virus d'Epstein-Barr (EBV) est associé à la maladie de Hodgkin, la question majeure restant de savoir s'il est un virus de passage ou s'il est un agent étiologique.

Dans cette étude, nous décrivons les conditions expérimentales pour la cytogenèse de cellules géantes à partir d'une culture de mononucléaires du sang périphérique. Les mononucléaires sont isolés du sang périphérique autologue et co-cultivés avec une suspension de cellules isolées obtenue à partir des ganglions lymphatiques de Hodgkin, dans une chambre de culture où les deux populations cellulaires sont isolées par filtration sur membrane microporeuse qui permet seulement le passage des cytokines et des virus.

Dans ces conditions, des cellules géantes sont formées dans la fraction des monucléaires, certaines étant morphologiquement indistinguables des cellules de Reed-Sternberg et de leurs variantes mononucléaires, les autres ressemblant beaucoup aux cellules géantes de Langhans. Certaines de ces cellules géantes sont ADN-EBV+ par hybridation in situ.

Ces résultats nous suggèrent que c'est l'activité biologique EBV-dépendante qui est responsable de la cytogenèse des cellules géantes d'origine lymphocytaire ou monocytaire, qu'elle soit induite par l'EBV et/ou par les cytokines.

References (78)

  • ParkerD.C.

    How does the helper T cell activate the resting B cell when it recognizes antigen on the B cell surface

  • SerkeS. et al.

    Lymphocyte activation by phytohaemagglutinin and pokeweed mitogen. Identification of proliferating cells by monoclonal antibodies

    J. Immunol. Meth.

    (1987)
  • SteinH. et al.

    The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that ReedSternberg cells and histiocytic malignancies are derived from activated lymphoid cells

    Blood

    (1985)
  • WolosJ.A.

    Factors in AMLR culture supernatant which mediate the cytotoxic T-cell response to hapten-altered self interaction with macrophages

    Clin. Immunol. Immunopath.

    (1986)
  • ZhengY. et al.

    Establishment and characterization of hybrid rat mast cells

    Exp. Cell. Res.

    (1991)
  • AndreseenR. et al.

    Origin of Reed-Sternberg cell in Hodgkin's disease

    N. Engl. J. Med

    (1989)
  • ArnoldE. et al.

    Formation of multinucleate giant cells from human monocyte precursors: mediation by a soluble protein from antigen and mitogen stimulated lymphocytes

    J. Exp. Med.

    (1982)
  • BaylissG.J. et al.

    An Epstein-Barr virus early protein induces cell fusion

  • Bentley LawrenceJ. et al.

    Extinction of muscle specific properties in somatic cell heterokaryons

    Develop. Biol.

    (1984)
  • BucksyP.

    Hodgkin's disease: the Sternberg-Reed cell

    Blut

    (1987)
  • BuyssensN. et al.

    The Sternberg-Reed cell: mononuclear, multinucleated or multilobated

    Virchov. Arch. A Path. Anat. Histol.

    (1980)
  • ChuW.S. et al.

    Inconsistency of the immunophenotype of ReedSternberg cells in simultaneous and consecutive specimens from the same patients

    Am. J. Pathol.

    (1992)
  • CossmanJ. et al.

    Rearranging antigen-receptor genes in enriched Reed-Sternberg cell fractions of Hodgkin's disease

    Hematol. Oncol.

    (1988)
  • DalgleishA.G. et al.

    A viral etiology for Hodgkin's disease

    Aust. NZ. J. Med.

    (1986)
  • DarlingtonG.J. et al.

    Expression of human hepatic genes in somatic cell hybrids

    Somatic Cell Genet.

    (1982)
  • DavidsonR.L.

    Gene expression in somatic cell hybrids

    Ann. Rev. Genet.

    (1974)
  • Donhvijsen-AntR. et al.

    Fatal Hodgkin and non-Hodgkin's lymphoma associated with persistent Epstein-Barr virus in four brothers

    Ann. Int. Med.

    (1988)
  • DrexlerH.G.

    Recent results on the biology of Hodgkin and Reed-Sternberg cells. —I. Biopsy material

    Leuk. Lymphoma

    (1992)
  • DrexlerH.G. et al.

    Genotypes and immuno-phenotypes of Hodgkin's disease derived cell lines

    Leukemia

    (1988)
  • DrexlerH.G. et al.

    Formation of multinucleated cells in a Hodgkin disease derived cell line

    Int. J. Cancer

    (1989)
  • FaliniB. et al.

    Expression of lymphoid associated antigens on Hodgkin's and Reed-Sternberg cells of Hodgkin's disease. An immunocytochemical study on lymph node cytospin using monoclonal antibody

    Histopathology

    (1987)
  • FavreM. et al.

    Caractères généraux du granulome malin, tirés de son étude anatomoclinique

    Ann. Anat. Pathol

    (1931)
  • FisherR.I. et al.

    Neoplastic cells obtained from Hodgkin's disease are potent stimulators of human primary mixed lymphocyte cultures

    J. Immunol.

    (1983)
  • GaulierA. et al.

    Do measles early giant cells result from fusion of non-infected cells ? An immunohisto-chemical and in situ hybridization study in a case of morbillous appendicitis

    Virchows Archiv. A. Pathol. Anat.

    (1991)
  • HarrisH. et al.

    The expression of genetic information: a study with hybrid animal cells

    J. Cell. Sci.

    (1969)
  • HendersonE.E. et al.

    Chemical carcinogen Epstein-Barr virus (EBV) synergism: EBV genome amplification and site-specific mutation during transformation

    Int. J. Cancer

    (1989)
  • HsuS.M. et al.

    The cultured Reed-Sternberg cells HDL M-1 and KM-H2 can be induced to become histiocyte-like cells. H-RS cells are not derived from lymphocytes

    Am. J. Pathol.

    (1990)
  • HsuS.M. et al.

    Phenotypic expression of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease

    Am. J. Pathol.

    (1985)
  • KadinM.E. et al.

    Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity Hodgkin's disease

    Am. J. Pathol

    (1988)
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