IL-28B/IFN-λ3 Drives Granzyme B Loading and Significantly Increases CTL Killing Activity in Macaques
IL-28B/IFN-λ3 Drives Granzyme B Loading and Significantly Increases CTL Killing Activity in Macaques
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DOI：
10.1038/mt.2010.118
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发表时间：
2010-09-01
影响因子：
12.4
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
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作者：
Morrow, Matthew P.;Yan, Jian;Weiner, David B.
III型/λ干扰素（IFN）是在不到十年前发现的，目前仍处于表征过程中。虽然以前的研究集中在小动物模型中IFN-λ 3（也称为白细胞介素（IL）-28 B）的功能，但尚不清楚这些功能是否会转化为更大，更相关的模型。因此，在本研究中，我们使用DNA疫苗接种作为研究IFN-λ 3对恒河猴适应性免疫应答的影响的方法。我们的研究结果首次表明，IFN-λ 3对抗原特异性CD 8 + T细胞功能具有显著影响，特别是在细胞毒性方面。通过CD 107 a和颗粒酶B共表达以及穿孔素释放测定，给予IFN-λ 3的动物的外周CD 8 + T细胞显示出显著增加的细胞毒性应答。此外，从接受IFN-λ 3的动物的肠系膜淋巴结（MLN）分离的CD 8 + T细胞在延长的抗原刺激后负载显著量的颗粒酶B，并诱导显著更多的颗粒酶B介导的肽脉冲靶细胞死亡。这些数据表明，IFN-λ 3是免疫系统的有效效应子，特别强调CD 8（+）T细胞杀伤功能，这保证了作为可能的免疫佐剂的进一步研究。
Type III/lambda interferons (IFNs) were discovered less than a decade ago and are still in the process of being characterized. Although previous studies have focused on the function of IFN-lambda 3 (also known as interleukin (IL)-28B) in a small animal model, it is unknown whether these functions would translate to a larger, more relevant model. Thus in the present study, we have used DNA vaccination as a method of studying the influence of IFN-lambda 3 on adaptive immune responses in rhesus macaques. Results of our study show for the first time that IFN-lambda 3 has significant influence on antigen-specific CD8+ T-cell function, especially in regards to cytotoxicity. Peripheral CD8+ T cells from animals that were administered IFN-lambda 3 showed substantially increased cytotoxic responses as gauged by CD107a and granzyme B coexpression as well as perforin release. Moreover, CD8+ T cells isolated from the mesenteric lymph nodes (MLN) of animals receiving IFN-lambda 3 loaded significant amounts of granzyme B upon extended antigenic stimulation and induced significantly more granzyme B-mediated cell death of peptide pulsed targets. These data suggest that IFN-lambda 3 is a potent effector of the immune system with special emphasis on CD8(+) T-cell killing functions which warrants further study as a possible immunoadjuvant.