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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 1020-1030
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
From the CRC Institute for Cancer Studies, University of Birmingham,
Birmingham, UK; the Department of Histopathology, Birmingham Heartlands
Hospital, Birmingham, UK; and the School of Health Sciences, University
of Wolverhampton, Wolverhampton, UK.
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.
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