Chow Kevin V, Delconte Rebecca B, Huntington Nicholas D, Tarlinton David M, Sutherland Robyn M, Zhan Yifan, Lew Andrew M
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;
J Immunol. 2016 Sep 1;197(5):2000-8. doi: 10.4049/jimmunol.1600181. Epub 2016 Jul 29.
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(-/-)γc(-/-) and scid γc(-/-)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.
尽管病原体相关分子模式的固有识别机制已得到明确界定,但同种异体细胞刺激如何引发固有反应仍不太清楚。在本文中,我们报告称,经静脉注射(以避免主要的医源性干扰)后,同种异体而非同基因白细胞可诱导宿主单核细胞来源的树突状细胞(moDC)迅速(1天后)积聚,而传统树突状细胞无任何增加。这在各种供体-宿主品系组合中均会发生,不需要MHC不匹配,并且可由包括B细胞、T细胞或NK细胞在内的各种供体细胞类型诱导。使用具有不同MHC的RAG(-/-)γc(-/-)和scid γc(-/-)小鼠,我们发现供体或宿主淋巴细胞的存在是必需的。当使用通过基因消融缺乏NK细胞的小鼠的脾细胞作为供体时,同种异体诱导的moDC积聚显著减少。这种moDC积聚的一个主要成分似乎是募集。我们的研究结果为固有免疫系统和适应性免疫系统在同种异体接触以及移植排斥过程中如何相互作用提供了新的见解。