Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3256-3261
Herpesvirus saimiri-transformed macaque T cells are tolerated and
do not cause lymphoma after autologous reinfusion
Andrea Knappe,
Gisela Feldmann,
Ulf Dittmer,
Edgar Meinl,
Thomas Nisslein,
Sabine Wittmann,
Kerstin Mätz-Rensing,
Thomas Kirchner,
Walter Bodemer, and
Helmut Fickenscher
From the Institut für Klinische und Molekulare
Virologie and the Institut für Pathologie,
Friedrich-Alexander-Universität Erlangen-Nürnberg,
Erlangen, Germany, and the Abteilung Virologie und Immunologie and the
Abteilung Tiermedizin und Primatenhaltung, Deutsches Primatenzentrum,
Göttingen, Germany.
Human T cells are transformed in vitro to stable growth after
infection with herpesvirus saimiri subgroup C strain C488, and they
retain their antigen-specific reactivity and other important functional
features of mature activated T lymphocytes. The virus persists as
nonintegrating episomes in human T cells under restricted viral gene
expression and without production of virus particles. This study
analyzes the behavior of herpesvirus-transformed autologous T cells
after reinfusion into the donor under close-to-human experimental conditions. T cells of 5 macaque monkeys were transformed to stable interleukin-2 dependent growth and were intravenously infused into the
respective donor. The animals remained healthy, without occurrence of
lymphoma or leukemia for an observation period of more than 1 year.
Over several months virus genomes were detectable in peripheral blood
cells and in cultured T cells by polymerase chain reaction. In naive
control animals, a high-dose intravenous infection rapidly induced
pleomorphic peripheral T-cell lymphoma. In contrast, monkeys were
protected from lymphoma after challenge infection if they had
previously received autologous T-cell transfusions. High levels of
antibodies against virus antigens were detectable after challenge
infection only. Taken together, herpesvirus-transformed T cells are
well tolerated after autologous reinfusion. This may allow us to develop a novel concept for adoptive T-cell mediated immunotherapy.
