Memory-Like Antigen-Specific Human NK Cells from TB Pleural Fluids Produced IL-22 in Response to IL-15 or Mycobacterium tuberculosis Antigens.
Memory-Like Antigen-Specific Human NK Cells from TB Pleural Fluids Produced IL-22 in Response to IL-15 or Mycobacterium tuberculosis Antigens.
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DOI：
10.1371/journal.pone.0151721
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Fu X;Yu S;Yang B;Lao S;Li B;Wu C
我们先前的结果表明，结核胸腔积液细胞(PFC)中的记忆样人自然杀伤(NK)细胞在卡介苗(BCG)刺激下产生大量干扰素-γ。此外，最近的研究表明，人类淋巴组织中有一个独特的NK细胞亚群，专门产生IL-22，这是一种促炎细胞因子，介导宿主对病原体的防御。然而，关于记忆样人NK细胞产生IL-22的特性的信息很少。在本研究中，我们发现IL-15和IL-12诱导的细胞因子可提高结核PFC中NK细胞产生IL-22的水平。此外，在卡介苗和结核分枝杆菌相关抗原的作用下，PFC的NK细胞产生IL-22，但不产生IL-17。更重要的是，PFC中产生IL-22的NK细胞亚群与产生干扰素-γ的NK细胞不同。分离CD45RO+或CD45RO-NK细胞，与自体单核细胞共同培养，用卡介苗刺激产生IL-22。结果表明，CD45RO+细胞产生IL-22水平明显高于CD45RO-NK细胞，而CD45RO-NK细胞无明显差异。卡介苗培养条件下，抗IL-12Rβ1单抗(2B10)部分抑制NK细胞IL-22的表达。BCG特异性产生IL-22的PFC的NK细胞表达CD45ROHighNKG2DHighranzyme BHigh。综上所述，我们的研究结果表明，记忆性抗原特异性的CD45RO+NK细胞可能通过产生IL-22参与结核分枝杆菌感染的回忆免疫应答，而IL-22在对抗结核分枝杆菌感染中起着至关重要的作用。
Our previous result indicated that memory-like human natural killer (NK) cells from TB pleural fluid cells (PFCs) produced large amounts of IFN-γ in response to Bacille Calmette Guerin (BCG). Furthermore, recent studies have shown that human lymphoid tissues harbored a unique NK cell subset that specialized in production of interleukin (IL)-22, a proinflammatory cytokine that mediates host defense against pathogens. Yet little information was available with regard to the properties of IL-22 production by memory-like human NK cells. In the present study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL-22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the subset of specific IL-22-producing NK cells were distinct from IFN-γ-producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured with autologous monocytes and stimulated with BCG for the production of IL-22. The result demonstrated that CD45RO+ but not CD45RO- NK cells produced significantly higher level of IL-22. Anti-IL-12Rβ1 mAbs (2B10) partially inhibit the expression of IL-22 by NK cells under the culture with BCG. Consistently, BCG specific IL-22-producing NK cells from PFCs expressed CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that memory-like antigen-specific CD45RO+ NK cells might participate in the recall immune response for M. tb infection via producing IL-22, which display a critical role to fight against M. tb.