Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
PLoS One. 2013 Apr 19;8(4):e61264. doi: 10.1371/journal.pone.0061264. Print 2013.
Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+) Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+) Tregs was also noted with a moderate increase in ECs but further increases of CD8(+) Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+) Tregs and increases in the levels of CD8(+) Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+) subsets in GIT as CD3(-/)CD8(+)/NKG2a(-) and CD3(+)/CD8(+)/NKG2a(+) subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine design.
在 SIV 感染中，缺乏对血液和相应胃肠道（GI）组织中合成 IL-17 的各种细胞谱系的频率和绝对数量的综合研究，以及它们与 CD4(+)Tregs、CD8(+)Tregs、总和 IFN-α合成浆细胞样树突状细胞（pDC）与血浆病毒载量的相关性。唯一可获得的 SIV 感染恒河猴（RM）被归类为精英控制器（EC），以及那些具有低、中、高病毒载量（HVL）的 RM，为解决这一问题提供了独特的机会。这些研究的结果表明，EC 表现出显著的逆转由 SIV 急性诱导的各种细胞谱系变化的能力。EC 与 HVL RM 之间在胃肠道组织（GIT）中的差异的重点是维持和/或增加 IL-17 合成 CD4、CD8 和 NK 细胞和 pDC 的水平，而与 HVL 猴子中 pDC 水平降低相关的 CD4(+)Tregs 和 IFN-α合成 pDC 的水平略有降低。与 HVL 猴子中 pDC 和 IFN-α合成 pDC 的水平增加相关，与 IL-17 合成 CD4、CD8 和 NK 细胞的水平降低相关，也注意到了 CD8(+)Tregs 的一个以前被低估的作用。在 EC 中，CD8(+)Tregs 适度增加，而在病毒血症猴子中，随着 VL 的增加，CD8(+)Tregs 进一步增加。还注意到血浆 VL 与 Th17、Tc17、NK-17、CD4(+)Tregs 水平降低和 CD8(+)Tregs、总和 IFN-α合成 pDC 水平增加之间存在正相关。这项研究还在 GIT 中确定了另外两个 IL-17(+)亚群，即 CD3(-/)CD8(+)/NKG2a(-)和 CD3(+)/CD8(+)/NKG2a(+)亚群。研究还表明，尽管持续上调 ISGs，但 IFN-α合成 pDCs 在慢性免疫激活中作用有限。最后，持续存在的固有免疫反应似乎与预后不良有关。这些发现为疫苗设计中重要的标志物提供了初步基础。
