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

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, ie, granzyme-B-expressing lymphocytes. H-RS cells in EBV(+) cases of Hodgkin's disease (HD) were found to express significantly higher levels of MHC 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. (C) 1996 by The American Society of Hematology.