Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant.
Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant.
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DOI：
10.1084/jem.20090247
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发表时间：
2009-07-06
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
--
作者：
Longhi MP;Trumpfheller C;Idoyaga J;Caskey M;Matos I;Kluger C;Salazar AM;Colonna M;Steinman RM
相对于其他几种Toll样受体（TLR）激动剂，我们发现聚肌苷酸：聚胞苷酸（聚IC）是最有效的佐剂的Th 1 CD 4 + T细胞反应的树突状细胞（DC）靶向HIV gag蛋白疫苗在小鼠中。为了确定在完整的动物和多克隆T细胞库的佐剂作用的机制，我们发现聚IC是最有效的诱导剂的I型干扰素（IFN），这是由DEC-205+ DC，单核细胞，和基质细胞。抗体阻断或缺失I型IFN受体表明IFN对DC的成熟和CD 4+免疫的发展是必需的。IFN-AR受体是DC对多聚IC应答的直接需要。STAT 1也是必需的，与I型IFN的要求一致，但不是II型IFN或IL-12 p40。I型IFN的诱导依赖于mda 5，但DC另外使用TLR 3。在骨髓嵌合体中，抗辐射和可能的非造血细胞是IFN的主要来源，但mda 5在骨髓源性和抗辐射宿主细胞中都是适应性反应所必需的。因此，多聚IC的佐剂作用需要广泛的先天I型IFN应答，其直接将DC的抗原呈递与获得性免疫联系起来。
Relative to several other toll-like receptor (TLR) agonists, we found polyinosinic:polycytidylic acid (poly IC) to be the most effective adjuvant for Th1 CD4+ T cell responses to a dendritic cell (DC)–targeted HIV gag protein vaccine in mice. To identify mechanisms for adjuvant action in the intact animal and the polyclonal T cell repertoire, we found poly IC to be the most effective inducer of type I interferon (IFN), which was produced by DEC-205+ DCs, monocytes, and stromal cells. Antibody blocking or deletion of type I IFN receptor showed that IFN was essential for DC maturation and development of CD4+ immunity. The IFN-AR receptor was directly required for DCs to respond to poly IC. STAT 1 was also essential, in keeping with the type I IFN requirement, but not type II IFN or IL-12 p40. Induction of type I IFN was mda5 dependent, but DCs additionally used TLR3. In bone marrow chimeras, radioresistant and, likely, nonhematopoietic cells were the main source of IFN, but mda5 was required in both marrow–derived and radioresistant host cells for adaptive responses. Therefore, the adjuvant action of poly IC requires a widespread innate type I IFN response that directly links antigen presentation by DCs to adaptive immunity.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
4.4
作者：
Havenar-Daughton, Colin;Kolumam, Ganesh A.;Murali-Krishna, Kaja
通讯作者：
Murali-Krishna, Kaja