J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/57/08 $2.00
Volume 186, Number 1, July 7, 1997 57-64

Resistance to Fas-mediated Apoptosis of Peripheral T Cells in Human T Lymphocyte Virus Type I (HTLV-I) Transgenic Mice with Autoimmune Arthropathy

By Shuji Kishi,^* Shinobu Saijyo, Masaaki Arai,^§ Shigeru Karasawa, Susumu Ueda, Mari Kannagi,^§ Yoichiro Iwakura, Masahiro Fujii,^§ and Shin Yonehara^¶

From the ^* Pharmaceutical Basic Research Laboratories JT Inc., Yokohama 236;  Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 163; ^§ Department of Immunotherapeutics, Medical Research Division, Tokyo Medical and Dental University, Tokyo 113;  Nippon Institute for Biological Science, Tokyo 198; ^¶ Institute for Virus Research, Kyoto University, Kyoto 606, Japan

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.

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