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Blood, 1 September 2002, Vol. 100, No. 5, pp. 1755-1764
IMMUNOBIOLOGY
B cells immortalized by a mini-Epstein-Barr virus encoding a
foreign antigen efficiently reactivate specific cytotoxic T
cells
Andreas Moosmann,
Naeem Khan,
Mark Cobbold,
Caroline Zentz,
Henri-Jacques Delecluse,
Gabi Hollweck,
Andrew D. Hislop,
Neil W. Blake,
Debbie Croom-Carter,
Barbara Wollenberg,
Paul A. H. Moss,
Reinhard Zeidler,
Alan B. Rickinson, and
Wolfgang Hammerschmidt
From the Department of Otorhinolaryngology,
Ludwig-Maximilians-Universität, Munich, Germany; GSF, Institute
for Clinical Molecular Biology and Tumor Genetics, Department of Gene
Vectors, and Clinical Cooperation Group Molecular Oncology, Munich,
Germany; Vaecgene Biotech, Munich, Germany; and the Cancer Research UK
Institute for Cancer Studies, University of Birmingham, Birmingham,
United Kingdom.
Lymphoblastoid cell lines (LCLs) are human B cells latently
infected and immortalized by Epstein-Barr virus (EBV). Presenting viral
antigens, they efficiently induce EBV-specific T-cell responses in
vitro. Analogous ways to generate T-cell cultures specific for other
antigens of interest are highly desirable. Previously, we constructed a
mini-EBV plasmid that consists of less than half the EBV genome, is
unable to cause virus production, but still immortalizes B cells in
vitro. Mini-EBV-immortalized B-cell lines (mini-LCLs) are efficiently
produced by infection of B cells with viruslike particles carrying only
mini-EBV DNA. Mini-EBV plasmids can be engineered to express an
additional gene in immortalized B cells. Here we present a mini-EBV
coding for a potent CD8+ T-cell antigen, the matrix
phosphoprotein pp65 of human cytomegalovirus (CMV). By means of this
pp65 mini-EBV, pp65-expressing mini-LCLs could be readily established
from healthy donors in a one-step procedure. We used these
pp65 mini-LCLs to reactivate and expand effector T cells from
autologous peripheral blood cells in vitro. When generated from
cytomegalovirus (CMV)-seropositive donors, these effector T-cell
cultures displayed strong pp65-specific HLA-restricted cytotoxicity. A
large fraction of CD8+ T cells with pp65 epitope
specificity was present in such cultures, as demonstrated by direct
staining with HLA/peptide tetramers. We conclude that the pp65
mini-EBV is an attractive tool for CMV-specific adoptive
immunotherapy. Mini-EBVs could also facilitate the generation of
T cells specific for various other antigens of interest.
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