Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice

Gerold Feuer, Jerome A. Zack, William J. Harrington, Ramon Valderama, Joseph D Rosenblatt, William Wachsman, Stephen M. Baird, Irvin S Y Chen

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Abstract

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.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalBlood
Volume82
Issue number3
StatePublished - Aug 1 1993
Externally publishedYes

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Human T-lymphotropic virus 1
SCID Mice
T-cells
T-Cell Lymphoma
Viruses
Adult T Cell Leukemia Lymphoma
Lymphocytes
Cells
Tumors
Neoplasms
Clone Cells
Tropical Spastic Paraparesis
Animals
Blood
T-Lymphocytes
Endemic Diseases
Proviruses
Spinal Cord Diseases
Virus Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma

ASJC Scopus subject areas

  • Hematology

Cite this

Feuer, G., Zack, J. A., Harrington, W. J., Valderama, R., Rosenblatt, J. D., Wachsman, W., ... Chen, I. S. Y. (1993). Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. Blood, 82(3), 722-731.

Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. / Feuer, Gerold; Zack, Jerome A.; Harrington, William J.; Valderama, Ramon; Rosenblatt, Joseph D; Wachsman, William; Baird, Stephen M.; Chen, Irvin S Y.

In: Blood, Vol. 82, No. 3, 01.08.1993, p. 722-731.

Research output: Contribution to journalArticle

Feuer, G, Zack, JA, Harrington, WJ, Valderama, R, Rosenblatt, JD, Wachsman, W, Baird, SM & Chen, ISY 1993, 'Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice', Blood, vol. 82, no. 3, pp. 722-731.
Feuer G, Zack JA, Harrington WJ, Valderama R, Rosenblatt JD, Wachsman W et al. Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. Blood. 1993 Aug 1;82(3):722-731.
Feuer, Gerold ; Zack, Jerome A. ; Harrington, William J. ; Valderama, Ramon ; Rosenblatt, Joseph D ; Wachsman, William ; Baird, Stephen M. ; Chen, Irvin S Y. / Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. In: Blood. 1993 ; Vol. 82, No. 3. pp. 722-731.
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