Kotani M, Tagawa Y, Iwakura Y
Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Japan.
Eur J Immunol. 1999 Jan;29(1):54-64. doi: 10.1002/(SICI)1521-4141(199901)29:01<54::AID-IMMU54>3.0.CO;2-M.
We previously reported that transgenic mice carrying the human T cell leukemia virus type I (HTLV-I) env-pX region (pX-transgenic mice) develop rheumatoid-like inflammatory arthropathy, and suggested involvement of autoimmunity in the pathogenicity. In this report, to elucidate pathogenesis of the arthritis, we investigated arthritogenic antigens in the joints. The TCR beta-chain variable region (Vbeta) repertoires in the lymphatic organs were normal in transgenic mice, however, specific Vbeta-positive T cells were expanded oligoclonally in the affected joints, suggesting that specific antigens, but not superantigens, were involved in the expansion of these T cells. These expanded T cells had the same TCR as those of lymph node T cells reactive to type II collagen (IIC). Moreover, these mice were susceptible to IIC-induced arthritis and oligoclonal T cells of the same Vbeta specificity as that found in spontaneously developed arthritic joint accumulated in the arthritic joints after immunization with IIC. These observations show that endogenous IIC is one of the arthritogenic antigens in the joint, suggesting tolerance break to this antigen in pX-transgenic mice.
我们之前报道过，携带人类I型T细胞白血病病毒（HTLV-I）env-pX区域的转基因小鼠（pX转基因小鼠）会发生类风湿样炎性关节炎，并提示自身免疫参与了其发病机制。在本报告中，为阐明关节炎的发病机制，我们研究了关节中的致关节炎抗原。转基因小鼠淋巴器官中的TCRβ链可变区（Vβ）库正常，然而，特定的Vβ阳性T细胞在受影响的关节中呈寡克隆性扩增，这表明特定抗原而非超抗原参与了这些T细胞的扩增。这些扩增的T细胞与对II型胶原（IIC）有反应的淋巴结T细胞具有相同的TCR。此外，这些小鼠易患IIC诱导的关节炎，在用IIC免疫后，与自发发生关节炎关节中发现的具有相同Vβ特异性的寡克隆T细胞会在关节炎关节中积聚。这些观察结果表明，内源性IIC是关节中的致关节炎抗原之一，提示pX转基因小鼠对该抗原的耐受性被打破。
