Fugo Kazunori, Ishizu Akihiro, Ikeda Hitoshi, Hayase Hiroko, Sugaya Toshiaki, Higuchi Masato, Tsuji Muneharu, Abe Asami, Suzuki Akira, Shibata Masahiko, Takahashi Toshiyuki, Yoshiki Takashi
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Am J Pathol. 2002 Sep;161(3):755-61. doi: 10.1016/S0002-9440(10)64234-4.
Necrotizing arteritis mimicking polyarteritis nodosa occurred in transgenic rats carrying the env-pX gene of human T-cell leukemia virus type I. To investigate the pathogenesis of necrotizing arteritis in these rats (env-pX rats), adoptive transfers of spleen cells and bone marrow cells were done from env-pX rats before they developed arteritis to nontransgenic rats. Necrotizing arteritis occurred in lethally irradiated nontransgenic rats reconstituted by env-pX spleen cells, thus indicating that the env-pX transgene in affected vessels may not be essential for the development of arteritis. In contrast, arteritis was not induced in nontransgenic recipients by adoptive transfers of env-pX bone marrow cells, which suggested that T cells derived from the env-pX thymus may play a role in the development of arteritis. To clarify if the process of differentiation of T cells in the env-pX thymus is crucial to develop necrotizing arteritis, reciprocal exchange of thymus frameworks was done between env-pX and nontransgenic rats. Necrotizing arteritis occurred in nontransgenic rats with an env-pX thymus framework, whereas development of arteritis was suppressed in env-pX rats in which the thymus framework was replaced with a nontransgenic one. This collective evidence shows that the thymus is directly associated with the development of necrotizing arteritis in env-pX rats.
携带I型人类T细胞白血病病毒env-pX基因的转基因大鼠发生了类似结节性多动脉炎的坏死性动脉炎。为了研究这些大鼠(env-pX大鼠)坏死性动脉炎的发病机制,在env-pX大鼠发生动脉炎之前,将其脾细胞和骨髓细胞过继转移到非转基因大鼠体内。由env-pX脾细胞重建的经致死性照射的非转基因大鼠发生了坏死性动脉炎,这表明受影响血管中的env-pX转基因可能对动脉炎的发展并非必不可少。相比之下,env-pX骨髓细胞的过继转移未在非转基因受体中诱导动脉炎,这表明源自env-pX胸腺的T细胞可能在动脉炎的发展中起作用。为了阐明env-pX胸腺中T细胞的分化过程对坏死性动脉炎的发展是否至关重要,在env-pX大鼠和非转基因大鼠之间进行了胸腺框架的相互交换。具有env-pX胸腺框架的非转基因大鼠发生了坏死性动脉炎,而胸腺框架被非转基因框架取代的env-pX大鼠中动脉炎的发展受到抑制。这些综合证据表明,胸腺与env-pX大鼠坏死性动脉炎的发展直接相关。