Abstract:
A series of transformed rabbit cell lines as derived by coculture of PBMC with cell lines chronically infected with human T-lymphotrophic virus type I (HTLV-I) and subsequently inoculated into mature outbred New Zealand white rabbits. Some of these cell lines were capable of killing rabbits in a dose-dependent manner within 6 days after a single iv injection. Within 3 days postinoculation, all rabbits inoculated with the lethal cell lines developed high fevers (up to 40.5 C), which were sustained for approx 2 days, followed by inability to regulate body temperatures, resulting in subnormal temperatures in most animals. Most of these animals became inactive, developed anorexia and lost as much as 15% of their body wt. Necropsy and histopathological examination of organs from some of these rabbits revealed atypical mononuclear leukemic cell infiltrates in lung, liver, spleen and within vascular lumina. Hematology and serum biochemical studies of rabbits that received sublethal doses of the lethal cell lines revealed abnormalities, including mild anemia and increased serum alanine aminotransferase. Certain HTLV-I cell lines killed and caused the observed signs and lesions, when as few as 1 x 10(8) cells were administered; other rabbit and human HTLV-I cell lines failed to kill at cell doses as high as 5 x 10(8). Preliminary examinations indicated that the lethal cell lines possessed many monocytelike characteristics, including phagocytosis of beads and adherence to plastic, while the other cell lines were nonadherent. Proviral sequence analysis revealed certain differences between lethal and nonlethal cell lines. Further analyses of these cell lines will include detail virus sequence comparisons and the evaluation of the role of cytokines in pathogenesis.
Keywords: Acute Disease Animal Body Temperature Regulation Cell Transformation, Viral *HTLV-I *Leukemia Rabbits ABSTRACT 930330
M9331100
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