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

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-I (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-I, All four HAM cell lines expressed the FAP-I 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 FAR-I, and this escape may be involved in the autoimmune condition observed in HAM/TSP patients.