Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens
Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens
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DOI：
10.4049/jimmunol.170.6.3171
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Moll, H
中科院分区：
文献类型：
--
作者：
Berberich, C;Ramírez-Pineda, JR;Moll, H
树突状细胞(DC)在负载微生物抗原和过继转移后，能够诱导对感染的免疫。这为以DC为基础的疫苗接种战略的发展提供了鼓励。然而，DC的佐剂作用机制尚不完全清楚，有必要确定用来武装DC的银。在本研究中，我们分析了DC来源的IL-12在诱导对大利什曼原虫抵抗中的作用，并评估了负载个别利什曼原虫抗原的DC的保护效果。用IL-12缺陷或野生型小鼠的抗原冲击的朗格汉斯细胞(LC)免疫易感动物，我们发现不能释放IL-12完全丧失了LC对利什曼病的中介保护能力。这表明供体LC来源的IL-12的可用性是发展保护性免疫的必要条件。此外，我们还检测了活化C激酶受体的利什曼原虫同源物、gp63、前鞭毛体表面抗原、动质体膜蛋白-11或真核核糖体延长和起始因子4a的利什曼原虫同源物的保护作用。结果表明，用经选择的分子定义寄生虫蛋白冲击的LC免疫小鼠，能够控制L的感染。此外，经特定利什曼原虫抗原冲击的DC的保护电位与其IL-12的表达水平相关。对DC疫苗接种后小鼠的细胞因子图谱的分析表明，保护与向Th1型反应的转变有关。总之，这些发现强调了致敏DC产生的IL-12的关键作用，并表明基于DC的亚单位疫苗的开发是可行的。
Upon loading with microbial Ag and adoptive transfer, dendritic cells (DC) are able to induce immunity to infections. This offers encouragement for the development of DC-based vaccination strategies. However, the mechanisms underlying the adjuvant effect of DC are not fully understood, and there is a need to identify Ag with which to arm DC. In the present study, we analyzed the role of DC-derived IL-12 in the induction of resistance to Leishmania major, and we evaluated the protective efficacy of DC loaded with individual Leishmania Ag. Using Ag-pulsed Langerhans cells (LC) from IL-12-deficient or wild-type mice for immunization of susceptible animals, we showed that the inability to release IL-12 completely abrogated the capacity of LC to mediate protection against leishmaniasis. This suggests that the availability of donor LC-derived IL-12 is a requirement for the development of protective immunity. In addition, we tested the protective effect of LC loaded with Leishmania homolog of receptor for activated C kinase, gp63, promastigote surface Ag, kinetoplastid membrane protein-11, or Leishmania homolog of eukaryotic ribosomal elongation and initiation factor 4a. The results show that mice vaccinated with LC that had been pulsed with selected molecularly defined parasite proteins are capable of controlling infection with L major. Moreover, the protective potential of DC pulsed with a given Leishmania Ag correlated with the level of their IL-12 expression. Analysis of the cytokine profile of mice after DC-based vaccination revealed that protection was associated with a shift toward a Th1-type response. Together, these findings emphasize the critical role of IL-12 produced by the sensitizing DC and suggest that the development of a DC-based subunit vaccine is feasible.