Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats

T. Oka, H. Sonobe, J. Iwata, I. Kubonishi, H. Satoh, M. Takata, Y. Tanaka, M. Tateno, H. Tozawa, S. Mori, T. Yoshiki, Y. Ohtsuki

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17 Citations (Scopus)

Abstract

Rat lymphoid cells, TARS-1, immortalized by coculture with adult T-cell leukemia cells, were intraperitoneally injected into 65 newborn, inbred WKAH/Hkm rats. In most of the rats, tumor nodules were discernible 7 to 15 days after transplantation but were completely rejected within 5 to 6 weeks. Two rats with no tumor nodules exhibited gait disturbances and paralysis of the hind legs 3 to 4 weeks after transplantation. Histological and hematological examinations revealed that a lymphoma/leukemia-like disease had developed in one of the two rats, and the T-lymphoid cell line WLeuk-1 was established from peripheral blood mononuclear cells from this rat. When the WLeuk-1 cells were transplanted into newborn WKAH/Hkm rats, the animals died of a lymphoma/leukemia-like disease within several weeks after transplantation, in contrast to their rejection of the TARS-1 cells. Southern blot and karyotype analyses revealed that WLeuk-1 cells had retained the marker chromosomes and human T-lymphotropic virus type I (HTLV-I) integration patterns of the parent cell line, TARS-1. The additional specific chromosome abnormalities 3p+, t(12;13), and Xq+ were found in the WLeuk-1 cells. Moreover, the expression of HTLV-I structural proteins was slightly depressed in WLeuk-1 cells, while that of the transacting factors p40(tax) and p21(x), but not that of p27(rex), was enhanced about fivefold compared with that in TARS-1. The transactivating function of p40(tax) was intact in WLeuk-1, as evidenced by enhanced interleukin-2 receptor alpha chain expression. These results suggest that aberrant expression of HTLV-I regulatory genes and alteration of cellular genes were associated with the phenotypic progression of the WLeuk-1 cell line.

Original languageEnglish
Pages (from-to)6686-6694
Number of pages9
JournalJournal of Virology
Volume66
Issue number11
DOIs
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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