Expression of FAP-1 (Fas-associated phosphatase) and resistance to Fas-mediated apoptosis in T cell lines derived from human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patients.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

AIDS Res Hum Retroviruses. 1998 Feb 10;14(3):261-7. Unique Identifier : AIDSLINE MED/98150881
Arai M; Kannagi M; Matsuoka M; Sato T; Yamamoto N; Fujii M; Department of Immunotherapeutics, Medical Research Division, Tokyo; Medical and Dental University, Yushima, Japan.

Abstract: Human T cell leukemia virus type 1 (HTLV-I) is the etiologic agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) with an autoimmune condition. We examined the sensitivity of HTLV-I-infected T cell lines to Fas-mediated apoptosis, which plays a critical role in the elimination of self-reactive T cells. Among 13 human T-cell lines, all 4 HAM-derived T cell lines and 4 of 6 non-HAM/HTLV-I T cell lines were resistant to apoptosis induced by anti-Fas antibody, whereas only 1 of 3 uninfected cell lines was resistant to apoptosis. The cell lines resistant to apoptosis expressed the viral tax gene and/or the cellular FAP-1 (Fas-associated phosphatase) gene, both of which inhibit Fas-mediated apoptosis in T cell lines. Although Tax is a transcriptional activator of a number of cellular genes, the expression of Tax in a T cell line did not induce the expression of FAP-1, suggesting that these two antiapoptotic proteins independently function in HTLV-I-infected cells. Seven of 10 HTLV-I-infected cell lines, compared with only 1 of 3 virus-negative cell lines, expressed FAP-1. All four HAM cell lines expressed the FAP-1 gene, and its level in these cells was higher than in other T cell lines. Our results suggest that virus-infected T cells escape Fas-mediated immune surveillance by the function of Tax and FAP-1, and this escape may be involved in the autoimmune condition observed in HAM/TSP patients.

Keywords: *Apoptosis *Carrier Proteins/PHYSIOLOGY *HTLV-I/PHYSIOLOGY *Paraparesis, Tropical Spastic/IMMUNOLOGY *Protein-Tyrosine-Phosphatase/PHYSIOLOGY *T-Lymphocytes/CYTOLOGY *T-Lymphocytes/VIROLOGY
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