CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.
CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.
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CD1反应性天然杀伤细胞是通过免疫特性部位发展全身耐受性的。
DOI：
10.1084/jem.190.9.1215
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发表时间：
1999-11-01
影响因子：
15.3
通讯作者：
Stein-Streilein, J
中科院分区：
文献类型：
--
作者：
Sonoda, K H;Exley, M;Snapper, S;Balk, S P;Stein-Streilein, J
全身耐受性可以通过将抗原引入免疫豁免部位（如眼睛）或直接引入血液中来引发。两种免疫途径均导致选择性缺乏全身迟发型超敏反应。虽然前房相关免疫偏离（ACAID）的实验动物模型发生在大多数小鼠品系，ACAID不能诱导在几个突变的小鼠品系，是巧合缺乏自然杀伤T（NKT）细胞。因此，这种免疫豁免位点介导的耐受模型为我们研究NKT细胞在耐受发展中的作用提供了一个很好的形式。以下数据表明，CD 1反应性NKT细胞是通过眼诱导的系统性耐受发展所必需的，如下：（a）CD 1敲除小鼠不能发展ACAID，除非它们用NKT细胞和CD 1+抗原呈递细胞一起重建;（B）体内NKT细胞的特异性抗体消除消除了ACAID的发展;和（c）野生型小鼠的抗-CD 1单克隆抗体治疗防止了ACAID的发展。值得注意的是，CD 1反应性NKT细胞不需要静脉内诱导的全身耐受，从而建立不同的机制介导的耐受性，通过这些途径接种的抗原的发展。NKT细胞在与免疫赦免位点相关的全身耐受性发展中的关键作用表明了涉及NKT细胞自身耐受性及其自身免疫缺陷的机制。
Systemic tolerance can be elicited by introducing antigen into an immune-privileged site, such as the eye, or directly into the blood. Both routes of immunization result in a selective deficiency of systemic delayed type hypersensitivity. Although the experimental animal model of anterior chamber–associated immune deviation (ACAID) occurs in most mouse strains, ACAID cannot be induced in several mutant mouse strains that are coincidentally deficient in natural killer T (NKT) cells. Therefore, this model for immune-privileged site–mediated tolerance provided us with an excellent format for studying the role of NKT cells in the development of tolerance. The following data show that CD1-reactive NKT cells are required for the development of systemic tolerance induced via the eye as follows: (a) CD1 knockout mice were unable to develop ACAID unless they were reconstituted with NKT cells together with CD1+ antigen-presenting cells; (b) specific antibody depletion of NKT cells in vivo abrogated the development of ACAID; and (c) anti-CD1 monoclonal antibody treatment of wild-type mice prevented ACAID development. Significantly, CD1-reactive NKT cells were not required for intravenously induced systemic tolerance, thereby establishing that different mechanisms mediate development of tolerance to antigens inoculated by these routes. A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in self-tolerance and their defects in autoimmunity.