Herpesvirus saimiri-transformed macaque T cells are tolerated and do not cause lymphoma after autologous reinfusion.
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.
Knappe
A
A
Institut für Klinische und Molekulare Virologie and the Institut für Pathologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Feldmann
G
G
Dittmer
U
U
Meinl
E
E
Nisslein
T
T
Wittmann
S
S
Mätz-Rensing
K
K
Kirchner
T
T
Bodemer
W
W
Fickenscher
H
H
D019264:Adoptive Transfer; D000818:Animals; D001804:Blood Transfusion, Autologous; D002472:Cell Transformation, Viral; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000209:etiology* / Q000473:pathology*; D008253:Macaca mulatta; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology