Neurotoxic activity in HTLV-I carrier lymphocyte culture

Abstract

A close association between human T-lymphotropic virus type I (HTLV-I) infection and a group of chronic myelopathies of unknown etiology has recently been established and the name “HTLV-I associated myelopathy” (HAM) has been coined. Although the mechanism of neural tissue damage in HAM remains virtually unknown, several lines of evidence suggest the involvement of a soluble factor(s) including cytokines and viral proteins in the disease process. In this study, we examined cytopathic effects of the supernatants from 6 HTLV-I carrier human T lymphocyte cell lines on 4 human and one murine neuroblastoma cell lines, and 2 human glioma cell lines. Among 6 lymphocyte cell culture supernatants, only 1 from MT-2 cell culture repeatedly exerted cytopathic effects on human neuroblastoma cells, particularly on IMR-32 cells: marked retraction of neurites leading to cellular clumping. This activity was neither abolished by treatment of the medium at 80°C for 30 min or by UV-irradiation, nor was it neutralized by anti-HTLV-I antibodies. The MT-2 supernatant also induced mild cytopathic changes in 2 other human neuroblastoma cell lines and 2 human glioma cell lines. This activity was abolished by treatment of the medium at 80°C for 30 min but not at 56°C for 30 min. Myelinated murine cerebellum explants and other cell lines showed no morphological changes when incubated with the MT-2 supernatant. In addition, the growth of THP-1 cells, a monocyte/macrophage lineage cell line, was remarkably suppressed when maintained in the MT-2 conditioned medium, accompanied by enhancement of phagocytotic activity. The THP-1 conditioned medium, on the other hand, suppressed tumor necrosis factor (TNF) activity detected in the MT-2 culture. These observations suggest that HTLV-I induced cytokines may directly act on neural cells, but their action appears to be regulated by the intricate interactions of lymphocytic and monocytic cells.