Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.
Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.
Kanno
H
H
Department of Pathology, Osaka University Medical School, Suita, Japan.
Naka
N
N
Yasunaga
Y
Y
Iuchi
K
K
Yamauchi
S
S
Hashimoto
M
M
Aozasa
K
K
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D016724:Empyema, Pleural / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000737:chemistry; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000737:chemistry
C066460:BCRF1 protein, Human herpesvirus 4; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014764:Viral Proteins; D016753:Interleukin-10