TNF-β produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts

F. Yu, Y. Itoyama, J. I. Kira, K. Fujihara, T. Kobayashi, T. Kitamoto, A. Suzumura, N. Yamamoto, Y. Nakajima, I. Goto

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Abstract

Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT- 2 supernatants were found to be dose dependent and were reduced by heat treatment at 100°C for 5 min, but not at 56°C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-α and rTNF-β also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30-kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-β mAb, although they were not blocked by anti-TNF-α mAb. In a Western blot assay, the 25- and 27-kDa bands of TNF-β were shown clearly in the HUT102 supernatant, although no TNF-α bands appeared. These findings suggest that TNF-β is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts.

Original languageEnglish
Pages (from-to)5930-5939
Number of pages10
JournalJournal of Immunology
Volume152
Issue number12
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yu, F., Itoyama, Y., Kira, J. I., Fujihara, K., Kobayashi, T., Kitamoto, T., Suzumura, A., Yamamoto, N., Nakajima, Y., & Goto, I. (1994). TNF-β produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts. Journal of Immunology, 152(12), 5930-5939.