DOES T-CELL TOLERANCE REQUIRE A DEDICATED ANTIGEN-PRESENTING CELL
DOES T-CELL TOLERANCE REQUIRE A DEDICATED ANTIGEN-PRESENTING CELL
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DOI：
10.1038/338074a0
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发表时间：
1989-03-02
期刊：
影响因子：
64.8
通讯作者：
GUERDER, S
中科院分区：
文献类型：
--
作者：
MATZINGER, P;GUERDER, S
大约30年前，伯内特提出免疫系统通过清除自身反应性淋巴细胞来维持自身耐受性。最近已经清楚的是，对于T细胞来说，这一步骤发生在胸腺，发育中的T细胞首先表达它们的抗原特异性受体。在这里，遇到抗原的t细胞消失了——如果它没有死亡，它至少会停止表达受体。相反，在外周，与抗原的接触会导致应答t细胞的激活和增殖。这种差异有两种可能的解释。要么是胸腺中的抗原呈递细胞与周围的抗原呈递细胞不同，它们不产生阳性信号，而是直接或间接杀死胸腺细胞5,6；或者T细胞本身是不同的，像未成熟的B细胞一样，在遇到抗原7,8后可能会死亡。我们测试了第一种可能性，发现来自脾脏的树突状细胞是成熟T细胞最有效的激活剂，也是年轻发育中的T细胞最有效的灭活剂。因此，决定t细胞是否应答或死亡的不是抗原提呈细胞，而是t细胞本身或其胸腺环境。
ALMOST 30 years ago Burnet proposed that the immune system maintained self-tolerance by deleting autoreactive lymphocytes1. Recently it has become clear that for T cells this step occurs in the thymus, where developing T cells first express their antigen-specific receptors2–4. Here a T-cell which encounters its antigen disappears—if it is not dead, it at least stops expressing its receptors. In the periphery by contrast, encounter with antigen leads to activation and proliferation of the responding T-cell. There are two possible explanations for this difference. Either the antigen-presenting cells in the thymus are different from those in the periphery and instead of producing positive signals they directly or indirectly kill the thymocytes5,6; or the T cells themselves are different, and like immature B cells, may die after encounter with antigen7,8. We tested the first possibility and found that dendritic cells from spleen, which are the most potent activators of mature T cells9, are also the most potent inactivators of young developing T cells. Thus it is not the antigen-presenting cell which determines whether a T-cell responds or dies, but the T-cell itself or its thymic environment.