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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7 July 1997
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July 07 1997
Resistance to Fas-mediated Apoptosis of Peripheral T Cells in Human T Lymphocyte Virus Type I (HTLV-I) Transgenic Mice with Autoimmune Arthropathy
Shuji Kishi,
Shuji Kishi
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
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Shinobu Saijyo,
Shinobu Saijyo
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
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Masaaki Arai,
Masaaki Arai
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
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Shigeru Karasawa,
Shigeru Karasawa
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
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Susumu Ueda,
Susumu Ueda
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
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Mari Kannagi,
Mari Kannagi
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
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Yoichiro Iwakura,
Yoichiro Iwakura
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
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Masahiro Fujii,
Masahiro Fujii
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
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Shin Yonehara
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
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Shuji Kishi
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
Shinobu Saijyo
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
Masaaki Arai
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
Shigeru Karasawa
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
Susumu Ueda
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
Mari Kannagi
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
Yoichiro Iwakura
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
Masahiro Fujii
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
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
Address correspondence to Shuji Kishi, Pharmaceutical Basic Research Laboratories JT Inc., 1-13-2 Fukuura, Kanazawa-ku, Yokohama 236, Japan. Phone: 81-45-786-7693; FAX: 81-45-786-7692.
1 Abbreviations used in this paper: AICD, activation-induced cell death; HAM/TSP, HTLV-I–associated myelopathy/tropical spastic paraparesis; HAAP, HTLV-I–associated arthropathy; SEB, staphylococcal enterotoxin.
Received:
March 05 1997
Revision Received:
April 17 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (1): 57–64.
Article history
Received:
March 05 1997
Revision Received:
April 17 1997
Citation
Shuji Kishi, Shinobu Saijyo, Masaaki Arai, Shigeru Karasawa, Susumu Ueda, Mari Kannagi, Yoichiro Iwakura, Masahiro Fujii, Shin Yonehara; Resistance to Fas-mediated Apoptosis of Peripheral T Cells in Human T Lymphocyte Virus Type I (HTLV-I) Transgenic Mice with Autoimmune Arthropathy. J Exp Med 7 July 1997; 186 (1): 57–64. doi: https://doi.org/10.1084/jem.186.1.57
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