Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function
Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function
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DOI：
10.1073/pnas.93.17.9102
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发表时间：
1996-08-20
影响因子：
11.1
通讯作者：
Stockinger, B
中科院分区：
文献类型：
--
作者：
Zal, T;Weiss, S;Stockinger, B
T细胞受体α链基因座处的等位基因排除是不完全的，导致产生表达两种T细胞受体的T细胞。已经提出了这种T细胞在自身免疫中的潜在参与[Padovan，E.，Casorati，G.，Dellabona，P.，Meyer，S.，Brockhaus，hi，& Lanzavecchia，A.，（1993）Science 262，422-424; Heath，W. R. &米勒，J，F，A，P，（1993）J，Exp. 178，1807-1811]，在此，我们表明第二T细胞受体的表达可以拯救具有自身特异性受体的T细胞免于胸腺缺失，并允许它们进入外周。通过在Rag 1（-/-）背景上组成型表达两种转基因T细胞受体产生的双受体T细胞通过维持低水平的自身特异性受体而对自身耐受，但自身反应性效应子功能（杀伤）可通过第二受体的激活来诱导。这就打开了这样一种可能性，即正常个体外周中携带两种受体的T细胞含有可在识别不相关的环境抗原后参与自身免疫效应子功能的脓毒性自身反应性细胞。
Allelic exclusion at the T-cell receptor alpha chain locus is incomplete resulting in the generation of T cells that express two T-cell receptors, The potential involvement of such T cells in autoimmunity has been suggested [Padovan, E,, Casorati, G,, Dellabona, P,, Meyer, S,, Brockhaus, hi, & Lanzavecchia, A, (1993) Science 262, 422-424; Heath, W. R. & Miller, J, F, A, P, (1993) J, Exp. Med. 178, 1807-1811], Here we show that expression of a second T-cell receptor can rescue T cells with autospecific receptors from thymic deletion and allow their exit into the periphery, Dual receptor T cells, created by constitutive expression of two transgenic T-cell receptors on a Rag1(-/-) background, are tolerant to self by maintaining low levels of autospecific receptor, but self-reactive effector function (killing) can be induced through activation via the second receptor, This opens the possibility that T cells carrying two receptors in the periphery of normal individuals contain putatively autoreactive cells that could engage in autoimmune effector functions after recognition of an unrelated environmental antigen.