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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

Steven P. Lee, Christothea M. Constandinou, Wendy A. Thomas, Debbie Croom-Carter, Neil W. Blake, Paul G. Murray, John Crocker and Alan B. Rickinson

Abstract

Approximately 40% of Hodgkin's disease (HD) cases in Western countries carry Epstein-Barr virus (EBV) in the malignant Hodgkin-Reed-Sternberg (H-RS) cells. HLA class I–restricted cytotoxic T 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 endogenously expressed antigens via the transporter associated with antigen processing (TAP)-dependent HLA class I pathway. We have assessed the antigen-presenting phenotype of H-RS cells in two ways. First, immunohistochemical analysis of 38 HD biopsies showed that H-RS cells were uniformly 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 showed that 4 of 5 could process and present EBV proteins to HLA class I–restricted EBV-specific CTL clones. Others have reported that human interleukin-10 (IL-10), which is expressed by H-RS cells in the majority of EBV-positive HD cases, can abrogate CTL recognition in some circumstances. 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-positive HD.

© 1998 by The American Society of Hematology.

  • Submitted February 2, 1998.
  • Accepted March 27, 1998.
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