Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge.

Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge.
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DOI:
10.4049/jimmunol.0801814
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发表时间:
2009-03-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Dutton RW
Dutton RW
中科院分区:
其他
文献类型:
--
作者:
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW

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我们在这里表明,IL-17分泌的CD 4 T(Th)17和CD 8 T(Tc)17效应细胞被发现在肺后的主要挑战与流感病毒A和阻断抗体IL-17增加体重减轻和减少生存。可以使用来自OT-I TCR转基因小鼠的初始CD 8 T细胞在体外产生Tcl 7效应子。T细胞数量扩增20倍,大多数分泌IL-17,但很少分泌IFN-γ。许多IL-17分泌细胞也分泌TNF,一些分泌IL-2。与Tc 1效应子相反,Tc 17对颗粒酶B、穿孔素信息和细胞溶解活性呈阴性。Tc 17表达孤儿核受体γt和FoxP 3的信息,但不表达T-bet和加塔-3转录因子。FoxP 3阳性、分泌IL-17和分泌IFN-γ的细胞代表三个独立的群体。IFN-γ、颗粒酶B、FoxP 3阳性细胞和IL-22阳性细胞主要来自记忆细胞,当由CD 44低而不是CD 8低T细胞产生时,数量减少。这种独特的CD 8效应T细胞亚群的细胞在转移到攻击后的幼稚受体后大大扩增,并可以保护它们免受致命的流感感染。Tc 17的保护作用伴随着比Tc 1注射小鼠更大的中性粒细胞流入肺,并且Tc 17效应子提供的保护作用较少依赖于穿孔素,但更多依赖于IFN-γ,这意味着涉及不同的机制。
We show here that IL-17-secreting CD4 T (Th)17 and CD8 T (Tc)17 effector cells are found in the lung following primary challenge with influenza A and that blocking Ab to IL-17 increases weight loss and reduces survival. Tc17 effectors can be generated in vitro using naive CD8 T cells from OT-I TCR-transgenic mice. T cell numbers expand 20-fold and a majority secretes IL-17, but little IFN-γ. Many of the IL-17-secreting cells also secrete TNF and some secrete IL-2. Tc17 are negative for granzyme B, perforin message, and cytolytic activity, in contrast to Tc1 effectors. Tc17 populations express message for orphan nuclear receptor γt and FoxP3, but are negative for T-bet and GATA-3 transcription factors. The FoxP3-positive, IL-17-secreting and IFN-γ-secreting cells represent three separate populations. The IFN-γ-, granzyme B-, FoxP3-positive cells and cells positive for IL-22 come mainly from memory cells and decrease in number when generated from CD44low rather than unselected CD8 T cells. Cells of this unique subset of CD8 effector T cells expand greatly after transfer to naive recipients following challenge and can protect them against lethal influenza infection. Tc17 protection is accompanied by greater neutrophil influx into the lung than in Tc1-injected mice, and the protection afforded by Tc17 effectors is less perforin but more IFN-γ dependent, implying that different mechanisms are involved.
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