CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells.

CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells.
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DOI:
10.1084/jem.20071451
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发表时间:
2007-10-29
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Di Santo JP
Di Santo JP
中科院分区:
其他
文献类型:
--
作者:
Vosshenrich CA;Lesjean-Pottier S;Hasan M;Richard-Le Goff O;Corcuff E;Mandelboim O;Di Santo JP

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产生干扰素的杀伤树突状细胞(ikdc)是最近被描述的CD11cloB220+细胞的一个子集,它与dc和自然杀伤(NK)细胞具有相同的表型和功能特性(Chan, c.w., E. Crafton, H.N. Fan, J. Flook, K. Yoshimura, M. Skarica, D. Brockstedt, T.W. Dubensky, M.F. Stins, L.L. Lanier等,2006)。Nat. Med. 12:207-213;Taieb, J., N. Chaput, C. Menard, L. Apetoh, E. Ullrich, M. Bonmort, M. Pequignot, N. Casares, M. Terme, C. Flament等。2006。Nat. Med. 12:214-219)。IKDC的发展似乎不寻常,因为使用白细胞介素(IL)-2受体β (IL- 2r β)链的细胞因子,而不是使用常见γ链(γc)的细胞因子,对于它们的产生是必需的。通过直接比较Rag2−/−γc−/y、Rag2−/−IL-2Rβ−/−、Rag2−/−IL-15−/−和Rag2−/−IL-2−/−小鼠,我们发现IKDC的发育与NK细胞的发育相似,都严格依赖IL-15。此外,ikdc一致表达nk特异性的Ncr-1转录本(编码NKp46),而Ncr1gfp/+γc−/y小鼠中不存在NKp46+细胞。在骨髓中发育的NK细胞和外周NK细胞上仔细检查了ikdc (CD11cloB220+MHC-II+)的区别特征。由于B220的表达是异质的,定义B220lo与B220hi的NK1.1+ NK细胞可以被认为是任意的,并且在携带不同水平B220的NK1.1+ NK细胞之间几乎没有发现表型差异。CD11c表达与B220或主要组织相容性复合体(MHC) II类(MHC-II)表达无关,大多数MHC-II+ NK1.1+细胞不表达B220,因此不是ikdc。最后,CD11c、MHC-II和B220水平在体外或体内激活后以增殖依赖的方式在NK1.1+细胞上上调。我们的数据表明,大多数CD11cloB220+“ikdc样”细胞代表活化的NK细胞。
Interferon-producing killer dendritic cells (IKDCs) are a recently described subset of CD11cloB220+ cells that share phenotypic and functional properties of DCs and natural killer (NK) cells (Chan, C.W., E. Crafton, H.N. Fan, J. Flook, K. Yoshimura, M. Skarica, D. Brockstedt, T.W. Dubensky, M.F. Stins, L.L. Lanier, et al. 2006. Nat. Med. 12:207–213; Taieb, J., N. Chaput, C. Menard, L. Apetoh, E. Ullrich, M. Bonmort, M. Pequignot, N. Casares, M. Terme, C. Flament, et al. 2006. Nat. Med. 12:214–219). IKDC development appears unusual in that cytokines using the interleukin (IL)-2 receptor β (IL-2Rβ) chain but not those using the common γ chain (γc) are necessary for their generation. By directly comparing Rag2−/−γc −/y, Rag2−/−IL-2Rβ−/−, Rag2−/−IL-15−/−, and Rag2−/−IL-2−/− mice, we demonstrate that IKDC development parallels NK cell development in its strict IL-15 dependence. Moreover, IKDCs uniformly express NK-specific Ncr-1 transcripts (encoding NKp46), whereas NKp46+ cells are absent in Ncr1gfp/+γc −/y mice. Distinguishing features of IKDCs (CD11cloB220+MHC-II+) were carefully examined on developing NK cells in the bone marrow and on peripheral NK cells. As B220 expression was heterogeneous, defining B220lo versus B220hi NK1.1+ NK cells could be considered as arbitrary, and few phenotypic differences were noted between NK1.1+ NK cells bearing different levels of B220. CD11c expression did not correlate with B220 or major histocompatibility complex (MHC) class II (MHC-II) expression, and most MHC-II+ NK1.1+ cells did not express B220 and were thus not IKDCs. Finally, CD11c, MHC-II, and B220 levels were up-regulated on NK1.1+ cells upon activation in vitro or in vivo in a proliferation-dependent fashion. Our data suggest that the majority of CD11cloB220+ “IKDC-like” cells represent activated NK cells.
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