Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease
Autor: | Hermann Herbst, Gerald Niedobitek, Hans-Dieter Foss, Harald Stein, Angelo Agathanggelou, Jens Samol, Iguaracyra Araujo, Hans Krause, Heike Klotzbach |
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Předmět: |
Cellular immunity
Herpesvirus 4 Human Immunology Molecular Sequence Data Biology medicine.disease_cause Biochemistry Polymerase Chain Reaction Virus Antigen hemic and lymphatic diseases medicine Cytotoxic T cell Humans Infectious Mononucleosis Interleukin 4 Lymphoma AIDS-Related Base Sequence Cell Biology Hematology medicine.disease Epstein–Barr virus Hodgkin Disease Lymphoma Interleukin-10 Interleukin 10 Cancer research Interleukin-4 |
Zdroj: | Europe PubMed Central |
Popis: | Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils. Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1- positive cells from cytotoxicity directed at viral antigens. |
Databáze: | OpenAIRE |
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