CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue
CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue
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CCL19 和 CCL28 通过调动反应性免疫细胞进入次级淋巴结和粘膜组织来增强对 HIV-1 gp140 的粘膜和全身免疫反应
DOI：
10.4049/jimmunol.1300120
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发表时间：
2013-08-15
影响因子：
4.4
通讯作者：
Hu, Qinxue
中科院分区：
文献类型：
--
作者：
Hu, Kai;Luo, Sukun;Hu, Qinxue
在粘膜入口处诱导广泛且有效的中和抗体仍然是大多数针对粘膜获得性病毒感染的疫苗的主要目标。选择能够促进全身和粘膜反应的适当佐剂对于制定有效的免疫策略至关重要。在这项研究中，我们研究了细胞因子 APRIL、CCL19 或 CCL28 的质粒共传递是否可以增强 Ag 诱导的针对 HIV-1 gp140 的免疫反应。我们的结果表明，pCCL19 和 pCCL28（而非 pAPRIL）显着增强 Ag 特异性全身和粘膜抗体反应。 pCCL19 或 pCCL28 增强的血清中 gp140 特异性抗体广泛分布在所有四种 IgG 亚类中，其中 IgG1 占主导地位。增强的全身和粘膜抗体显示出针对同源和异源 HIV-1 的中和活性增加，并且效力与 gp140 特异性血清 IgG 和阴道 IgA 水平相关。对脾细胞产生的 gp140 特异性细胞因子的测量表明，pCCL19 和 pCCL28 增强了平衡的 Th1/Th2 反应。 pCCL19 和 pCCL28 还增加结直肠粘膜组织中的 IgA+ 细胞。 pCCL19 共递送导致肠系膜淋巴结中 CCR7+ CD11c+ 细胞以及脾脏中 CCR7+ CD11c+ 细胞和 CCR7+ CD3e+ 细胞增加，而 pCCL28 共递送导致脾和肠系膜淋巴结中 CCR10+ CD19+ 细胞增加。总之，我们的数据表明 pCCL19 和 pCCL28 可以增强 HIV-1 包膜特异性全身和粘膜抗体反应以及 T 细胞反应。这种增强似乎与反应性免疫细胞通过与相应受体相互作用而动员到次级淋巴器官和粘膜组织有关。
Induction of broad and potent neutralizing Abs at the mucosal portals of entry remains a primary goal for most vaccines against mucosally acquired viral infections. Selection of appropriate adjuvants capable of promoting both systemic and mucosal responses will be crucial for the development of effective immunization strategies. In this study, we investigated whether plasmid codelivery of cytokines APRIL, CCL19, or CCL28 can enhance Ag-induced immune responses to HIV-1 gp140. Our results demonstrated that pCCL19 and pCCL28, but not pAPRIL, significantly enhanced Ag-specific systemic and mucosal Ab responses. gp140-specific Abs in serum enhanced by pCCL19 or pCCL28 were broadly distributed across all four IgG subclasses, of which IgG1 was predominant. The enhanced systemic and mucosal Abs showed increased neutralizing activity against both homologous and heterologous HIV-1, and potency correlated with gp140-specific serum IgG and vaginal IgA levels. Measurement of gp140-specific cytokines produced by splenocytes demonstrated that pCCL19 and pCCL28 augmented balanced Th1/Th2 responses. pCCL19 and pCCL28 also increased IgA+ cells in colorectal mucosal tissue. pCCL19 codelivery resulted in an increase of CCR7+ CD11c+ cells in mesenteric lymph nodes and both CCR7+ CD11c+ cells and CCR7+ CD3e+ cells in spleen, whereas pCCL28 codelivery resulted in an augment of CCR10+ CD19+ cells in both spleen and mesenteric lymph nodes. Together, our data indicate that pCCL19 and pCCL28 can enhance HIV-1 envelope–specific systemic and mucosal Ab responses, as well as T cell responses. Such enhancements appear to be associated with mobilization of responsive immunocytes into secondary lymphoid organs and mucosal tissues through interactions with corresponding receptors.