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Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that
lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+
Hodgkin's disease
AP Sing, RF Ambinder, DJ Hong, M Jensen, W Batten, E Petersdorf and PD Greenberg
Division of Oncology, University of Washington, Seattle 98195-6527, USA.
A subset of Hodgkin's disease (HD) patients have detectable Epstein- Barr
virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R- S cells
express only a limited set of latent EBV proteins, but only LMP1 and LMP2
can potentially elicit a CD8+ cytotoxic T-lymphocyte (CTL) response. We
have evaluated if either of these proteins could be used as targets for
specific adoptive T-cell therapy for EBV-positive (EBV+) HD. The success of
this strategy requires that R-S cells are susceptible to lysis by CD8+ CTL,
and that CTL specific for LMP1 and LMP2 can be detected and potentially
amplified in HD patients. Antigen presentation and CTL sensitivity was
evaluated with an in vitro maintained, phenotypically representative R-S
cell line, HDLM-2. The R- S cells were able to process and present viral
proteins, and to be efficiently lysed by specific CTL in a Class
I-restricted manner. Since CTL responses to LMP1 and LMP2 do not represent
the dominant responses to EBV, we examined if CTL clones specific for these
proteins could be isolated despite the presence of weak or nondetectable
responses in polyclonal T-cell lines. LMP-specific clones were generated
from individuals either by cloning from the polyclonal EBV-reactive T-cell
lines or by direct stimulation of peripheral blood mononuclear cells (PBMC)
with cells expressing LMP1 or LMP2 as the only EBV protein. Our ability to
isolate CTL specific for LMP proteins from individuals with HD and the
sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of
specific adoptive immunotherapy represents a viable strategy for the subset
of HD patients with EBV+ tumors.
Volume 89,
Issue 6,
pp. 1978-1986,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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