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Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in
severe combined immunodeficient mice and characterization of the cells
proliferating in vivo
K Imada, A Takaori-Kondo, T Akagi, K Shimotohno, K Sugamura, T Hattori, H Yamabe, M Okuma and T Uchiyama
First Department of Internal Medicine, Kyoto University, Japan.
The mechanism involved in leukemogenesis and neoplastic cell growth of
adult T-cell leukemia (ATL) still remains unclear. We examined the
tumorigenicity of human T-cell leukemia virus type I (HTLV-I)-infected cell
lines in an in vivo cell proliferation model using severe combined
immunodeficient (SCID) mice. Eleven HTLV-I-infected cell lines were
injected into SCID mice and we found that 4 of them were capable of
proliferating in SCID mice. Three of four transplantable cell lines are
derived from the leukemic cell clone and 6 of 6 HTLV-I-infected cell lines
of nonleukemic cell origin could not engraft in SCID mice. Interestingly,
it was shown that some HTLV-I-infected and interleukin-2 (IL-2)-dependent
cell lines could successfully engraft in SCID mice. The expression of IL-2
mRNA was not detected in these cell lines growing either in vivo or in
vitro. HTLV-I viral products were not detected in 3 of 4 transplantable
cell lines proliferating in vivo. Peripheral blood T cells immortalized by
introduction of tax gene of HTLV-I were found to have no tumorigenic
potential in SCID mice. These data suggest that (1) HTLV-I-infected cell
lines of nonleukemic cell origin do not have enough leukemogenic changes to
acquire the tumorigenic potential in SCID mice; (2) the IL-2 autocrine
mechanism is not directly involved in the tumor cell growth; (3) viral gene
expression is not needed for the maintenance of neoplastic cell growth; and
(4) the expression of tax gene is not sufficient for the neoplastic cell
growth in vivo.
Volume 86,
Issue 6,
pp. 2350-2357,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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