Resistance to fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus type I (HTLV-I) transgenic mice with autoimmune arthropathy.
Transgenic mice carrying the env-pX region of human T lymphocyte virus type I (HTLV-I) develop autoimmune arthropathy in high incidence. Adopting the approach that Fas-mediated apoptosis has a critical function in the elimination of self-reactive T cells, we examined the involvement of this apoptosis in the induction of autoimmunity in HTLV-I transgenic mice. Splenic T cells derived from the transgenic mice were more resistant to apoptosis induced by anti-Fas mAb than those of the nontransgenic mice, whereas no appreciable difference in apoptosis was detected for thymocytes from either mouse's type. The resistance of transgenic T cells may be due to Tax coded in the pX region, since Tax mediates the inhibition of anti-Fas- induced apoptosis in mature T cell line, Jurkat. Among the transgenic mice, the extent of the resistance to Fas-mediated apoptosis was further enhanced in transgenic T cells with disease. These results suggest that the escape of self-reactive T cells from Fas-mediated apoptosis in the periphery, is critical for the development of autoimmune arthropathy in HTLV-I transgenic mice.
Kishi
S
S
Pharmaceutical Basic Research Laboratories JT Inc., Yokohama 236, Japan.
Saijyo
S
S
Arai
M
M
Karasawa
S
S
Ueda
S
S
Kannagi
M
M
Iwakura
Y
Y
Fujii
M
M
Yonehara
S
S
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007592:Joint Diseases / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor / Q000276:immunology*
D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor; C072343:pX protein, Human T-lymphotropic virus 1