Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells

Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells
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DOI:
10.4049/jimmunol.1600181
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发表时间:
2016-09-01
影响因子:
4.4
通讯作者:
Lew, Andrew M.
Lew, Andrew M.
中科院分区:
医学2区
文献类型:
--
作者:
Chow, Kevin V.;Delconte, Rebecca B.;Lew, Andrew M.

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尽管病原体相关分子模式的先天识别机制已经得到很好的定义,但同种异体细胞刺激如何引起先天反应仍然不太清楚。在本文中,我们报告了我。v.转移(以避免主要的医源性干扰),同种异体而非同系白细胞可以诱导宿主单核细胞衍生的树突细胞(moDC)的快速(1天后)积累,而常规DC没有任何增加。这发生在各种供体-宿主菌株组合中,不需要MHC错配,并且可以由各种供体细胞类型(包括B细胞、T细胞或NK细胞)诱导。使用具有不同MHC的RAG(-/-)gamma c(-/-)和scid gamma c(-/-)小鼠,我们发现需要供体或宿主淋巴样细胞的存在。当使用来自通过基因消融而缺乏NK细胞的小鼠的脾细胞作为供体时,同种异体诱导的moDC积累显著减少。这种moDC积累的一个主要组成部分似乎是招募。我们的研究结果提供了新的见解,先天和适应性免疫系统如何在同种异体遭遇,从而移植排斥反应可能相互作用。
Although the mechanisms governing the innate recognition of pathogen-associated molecular patterns have been well defined, how allogeneic cellular stimuli evoke innate responses remains less so. In this article, we report that upon i. v. transfer (to avoid major iatrogenic interference), allogeneic but not syngeneic leukocytes could induce a rapid (after 1 d) accumulation of host monocyte-derived dendritic cells (moDCs) without any increase in conventional DCs. This occurred in various donor-host strain combinations, did not require MHC mismatch, and could be induced by various donor cell types including B cells, T cells, or NK cells. Using RAG(-/-) gamma c(-/-) and scid gamma c(-/-) mice with different MHC, we found that the presence of either donor or host lymphoid cells was required. Alloinduced moDC accumulation was significantly reduced when splenocytes from mice deficient in NK cells by genetic ablation were used as donors. A major component of this moDC accumulation appears to be recruitment. Our findings provide new insights into how the innate and adaptive immune system may interact during allogeneic encounters and thus transplant rejection.