Ridge J P, Di Rosa F, Matzinger P
Ghost lab, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, NIAID/NIH, Bethesda, Maryland 20892, USA.
Nature. 1998 Jun 4;393(6684):474-8. doi: 10.1038/30989.
To generate an immune response, antigen-specific T-helper and T-killer cells must find each other and, because they cannot detect each other's presence, they are brought together by an antigen-loaded dendritic cell that displays antigens to both. This three-cell interaction, however, seems nearly impossible because all three cell types are rare and migratory. Here we provide a potential solution to this conundrum. We found that the three cells need not meet simultaneously but that the helper cell can first engage and 'condition' the dendritic cell, which then becomes empowered to stimulate a killer cell. The first step (help) can be bypassed by modulation of the surface molecule CD40, or by viral infection of dendritic cells. These results may explain the long-standing paradoxical observation that responses to some viruses are helper-independent, and they evoke the possibility that dendritic cells may take on different functions in response to different conditioning signals.
为了产生免疫反应，抗原特异性辅助性T细胞和杀伤性T细胞必须相互找到对方，然而由于它们无法检测到彼此的存在，因此由负载抗原的树突状细胞将它们聚集在一起，该树突状细胞会向两者展示抗原。然而，这种三细胞相互作用似乎几乎是不可能的，因为这三种细胞类型都很罕见且具有迁移性。在这里，我们提供了一个解决这一难题的潜在方案。我们发现这三种细胞不必同时相遇，辅助性T细胞可以首先与树突状细胞结合并使其“预处理”，然后树突状细胞就有能力刺激杀伤性T细胞。第一步（辅助作用）可以通过调节表面分子CD40或通过树突状细胞的病毒感染来绕过。这些结果可能解释了长期存在的矛盾观察结果，即对某些病毒的反应是不依赖辅助性T细胞的，并且它们引发了一种可能性，即树突状细胞可能会根据不同的预处理信号发挥不同的功能。
