HIGH-INCIDENCE OF SPONTANEOUS AUTOIMMUNE ENCEPHALOMYELITIS IN IMMUNODEFICIENT ANTIMYELIN BASIC-PROTEIN T-CELL RECEPTOR TRANSGENIC MICE
HIGH-INCIDENCE OF SPONTANEOUS AUTOIMMUNE ENCEPHALOMYELITIS IN IMMUNODEFICIENT ANTIMYELIN BASIC-PROTEIN T-CELL RECEPTOR TRANSGENIC MICE
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DOI：
10.1016/0092-8674(94)90419-7
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发表时间：
1994-08-12
期刊：
影响因子：
64.5
通讯作者：
TONEGAWA, S
中科院分区：
文献类型：
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作者：
LAFAILLE, JJ;NAGASHIMA, K;TONEGAWA, S
我们已经培育出了对髓鞘碱性蛋白（MBP）具有特异性的T细胞受体（TCR）转基因小鼠（T/R(+)），并将它们与RAG - 1基因缺陷小鼠杂交，以获得具有表达转基因TCR的T细胞但没有其他淋巴细胞的小鼠（T/R(-)）。T/R(+)和T/R(-)小鼠在淋巴结和脾脏中都携带大量可能诱发脑脊髓炎的CD4(+)抗MBP T细胞。这些细胞在体外对MBP有反应，但在体内没有活化的迹象。然而，约14%的H - 2(u) T/R(+)小鼠和100%的H - 2(u) T/R(-)小鼠在12个月内发生了自发性实验性自身免疫性脑脊髓炎（EAE）。这些数据表明，在没有任何其他淋巴细胞的情况下，EAE可由CD4(+)抗MBP T细胞介导，并且存在于T/R(+)小鼠中但不存在于T/R(-)小鼠中的非转基因淋巴细胞具有保护作用。这些数据还表明，自发性EAE可能是由神经系统中CD4(+)抗MBP细胞的原位活化所引发的。
We have generated TCR transgenic mice (T/R(+)) specific for myelin basic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mice (T/R(-)) that have T cells expressing the transgenic TCR but no other lymphocytes. Both T/R(+) and T/R(-) mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4(+) anti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, similar to 14% of H-2(u) T/R(+) and 100% of H-2(u) T/R(-) mice developed spontaneous experimental autoimmune encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be mediated by CD4(+) anti-MBP T cells in the absence of any other lymphocytes and that nontransgenic lymphocytes that are present in T/R(+) but absent in T/R(-) mice have a protective effect. The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4(+) anti-MBP cells in the nervous system.