Matter Matthias S, Claus Christina, Ochsenbein Adrian F
Tumor Immunology, Department of Clinical Research, University of Berne, Bern, Switzerland.
Eur J Immunol. 2008 Jul;38(7):1847-56. doi: 10.1002/eji.200737824.
CD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27(high) whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27(-/-) memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory.
在CD8⁺T淋巴细胞致敏过程中，CD4⁺T细胞的辅助作用赋予了再次遇到抗原时进行最佳二次扩增的能力。得到辅助的记忆性CD8⁺T细胞在再次接触抗原时会迅速扩增，即使在没有T细胞辅助的情况下也是如此，并且在抵御再次感染方面效率最高。相比之下，未得到辅助的记忆性CTL可以介导效应功能，但二次扩增会减少。CD4⁺T细胞在致敏过程中如何指导CD8⁺记忆性T细胞进行有效的二次扩增，目前尚未得到详细解决。在这里，我们表明，感染淋巴细胞性脉络丛脑膜炎病毒后的记忆性CTL是CD27高表达的，而在没有CD4⁺T细胞的情况下致敏的记忆性CTL的CD27表达降低。未得到辅助的记忆性CTL产生的IL-2量低，并且在体外用肽重新刺激后不能有效地扩增。用单克隆抗体进行的阻断实验以及使用CD27敲除的记忆性CTL表明，重新刺激期间CD27的连接增加了自分泌IL-2的产生和二次扩增。因此，调节记忆性CTL上的CD27表达是CD4⁺T细胞控制CTL记忆的一种新机制。
