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Establishment of human T-cell leukemia virus type I T-cell lymphomas in
severe combined immunodeficient mice
G Feuer, JA Zack, WJ Harrington , R Valderama, JD Rosenblatt, W Wachsman, SM Baird and IS Chen
Department of Microbiology & Immunology, UCLA School of Medicine 90024-
1678.
Human T-cell leukemia virus type I (HTLV-I) is recognized as the etiologic
agent of adult T-cell leukemia (ATL), a disease endemic in certain regions
of southeastern Japan, Africa, and the Caribbean basin. Although HTLV-I can
immortalize T lymphocytes in culture, factors leading to tumor progression
after HTLV-I infection remain elusive. Previous attempts to propagate the
ATL tumor cells in animals have been unsuccessful. Severe combined
immunodeficient (SCID) mice have previously been used to support the
survival of human lymphoid cell populations when inoculated with human
peripheral blood lymphocytes (PBL). SCID mice were injected
intraperitoneally with PBL from patients diagnosed with ATL,
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or
from asymptomatic HTLV-I-seropositive patients. Many of these mice become
persistently infected with HTLV-I. Furthermore, after human reconstitution
was established in these mice, HTLV-I-infected cells displayed a
proliferative advantage over uninfected human cells. Lymphoblastic
lymphomas of human origin developed in animals injected with PBL from two
ATL patients. The tumor cells represented outgrowth of the original ATL
leukemic clone in that they had monoclonal or oligoclonal integrations of
the HTLV-I provirus identical to the leukemic clone and predominantly
expressed the cell surface markers, CD4 and CD25. In contrast, cell lines
derived by HTLV immortalization of T cells in vitro did not persist or form
tumors when inoculated into SCID mice, indicating differences between in
vitro immortalized cells and ATL leukemic cells. This system represents the
first small animal model to study HTLV-I tumorigenesis in vivo.
Volume 82,
Issue 3,
pp. 722-731,
08/01/1993
Copyright © 1993 by The American Society of Hematology
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