ANTIGEN-PRESENTING PHENOTYPE OF HODGKIN-REED-STERNBERG CELLS - ANALYSIS OF THE HLA CLASS-I PROCESSING PATHWAY AND THE EFFECTS OF INTERLEUKIN-10 ON EPSTEIN-BARR VIRUS-SPECIFIC CYTOTOXIC T-CELL RECOGNITION

Approximately 40% of Hodgkin's disease (HD) cases in Western countries carry Epstein-Barr virus (EBV) in the malignant Hodgkin-Reed-Sternber g (H-RS) cells. HLA class I-restricted cytotoxic a lymphocytes (CTLs) with specificity for Viral antigens expressed in H-RS cells therefore have therapeutic potential. However, a prerequisite for CTL therapy is that the tumor target be capable of processing and presenting endogen ously expressed antigens via the transporter associated with antigen p rocessing (TAP)-dependent HLA class I pathway. We have assessed the an tigen-presenting phenotype of H-RS cells in two ways. First, immunohis tochemical analysis of 38 Ho biopsies showed that H-RS cells were unif ormly TAP1/TAP2-positive and expressed HLA class I in the majority (18 of 24, 75%) of EBV-positive cases compared with only 4 of 14 (29%) of EBV-negative cases. Second, using a panel of 5 H-RS cell lines, we sh owed that 4 of 5 could process and present EBV proteins to HLA class I -restricted EBV-specific CTL clones. Others have reported that human i nterleukin-10 (IL-10), which is expressed by H-RS cells in the majorit y of EBV-positive HD cases, can abrogate CTL recognition in some circu mstances. However, IL-10 pretreatment of the H-RS lines or of the EBV- specific CTLs had no such effect in this system. These results support the possibility that EBV-specific CTLs may be used to treat virus-pos itive HD. (C) 1998 by The American Society of Hematology.