Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease

Abstract

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.

Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation

“…The observation that many of the transformation-associated ISGs which we have identified are overexpressed in the malignant HRS cells of HL ( Figure 5, Table 6), and that a substantial number of these are also concordantly up-regulated by LMP1 or LMP2A in normal GC B cells (Table 7), suggests this maybe a profitable line of inquiry. Although IL-4 is not usually expressed in HL [60][61][62], IL13 with which it shares functional receptors [63,64] and remarkably similar biological functions is expressed [65]. Furthermore, proliferation of HL-derived lines in vitro and in vivo is reduced by antibodies to IL-13 or by decoy receptor molecules, suggesting that IL-13 can act as an autocrine growth-factor in HL [66,67].…”

Hodgkin’s Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells

“…Conversely, recent studies have indicated that HLILs produce hardly any Th2 cytokines (IL-4 or IL-13) [5,6]. Moreover, another study showed that HLILs produce IL-10 but not IL-4, raising the possibility that HLILs might be regulatory T (Treg) cells [7].…”

Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease

“…IL-10, a T-helper type 2 cytokine, has a suppressive effect on cell-mediated immunity (5)(6)(7) . Il-10 production was reported to be elevated in certain tumors, such as non-small cell lung cancer, B-cell lymphomas and Hodgkin disease, renal cell, ovarian, colon, and skin cancers (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) . Also, in cervical cancer and CIN, the presence as well as the progression of cervical cancer has been associated with increased IL-10 serum levels (18,19) .…”