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Analysis of major histocompatibility complex class I expression on Reed- Sternberg cells in relation to the cytotoxic T-cell response in Epstein- Barr virus-positive and -negative Hodgkin's disease

JJ Oudejans, NM Jiwa, JA Kummer, A Horstman, W Vos, JP Baak, PM Kluin, P van der Valk, JM Walboomers and CJ Meijer

Abstract

To get insight into the failure of the immune system to eradicate Epstein-Barr virus (EBV) harboring Hodgkin and Reed-Sternberg cells (H- RS cells), expressing the latent membrane protein 1 (LMP1), we analyzed major histocompatibility complex (MHC) class I expression on H-RS cells in relation to the presence of activated cytotoxic cells, i.e., granzyme-B-expressing lymphocytes. H-RS cells in EBV+ cases of Hodgkin's disease (HD) were found to express significantly higher levels of MCH class I heavy- and light-chain molecules compared with EBV- HD cases. When low levels of MHc class I expression were found (mainly in EBV- cases), these were not associated with low levels of the transporter protein associated with antigen presentation 1 (TAP-1). The relatively high levels of MHC class I expression in H-RS cells in EBV+ HD cases were accompanied by significantly higher numbers of activated cytotoxic T lymphocytes (CTLs) as shown by the presence of increased numbers of CD8 and granzyme B+ lymphocytes. However, these cells were only sporadically detected in the close vicinity of the H-RS cells. These data suggest that mechanisms other than downregulation of MHC class I or TAP-1 expression on H-RS cells are involved in the failure of the immune system to eradicate EBV harboring H-RS cells. Probably, the function of activated CTLs is locally inhibited by the H- RS cells or by reactive cells in the vicinity of the H-RS cells.