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-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.
Arai
M
M
Department of Immunotherapeutics, Medical Research Division, Tokyo Medical and Dental University, Yushima, Japan.
Kannagi
M
M
Matsuoka
M
M
Sato
T
T
Yamamoto
N
N
Fujii
M
M
D017209:Apoptosis; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000821:virology*; D019014:fas Receptor / Q000502:physiology
D002352:Carrier Proteins; D016356:Gene Products, tax; D019014:fas Receptor; D005047:Etoposide; D004317:Doxorubicin; C516742:PTPN13 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases