Department of Clinical Sciences, University of Milan, Milan, Italy.
PLoS One. 2011;6(10):e26979. doi: 10.1371/journal.pone.0026979. Epub 2011 Oct 31.
Mucosae-associated epithelial chemokine (MEC or CCL28) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs) in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB) Virus-like particles (VLPs). Mice receiving either HIV-1(IIIB) VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+) splenocytes of HIV-1(IIIB) VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB) VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines.
黏膜相关上皮趋化因子（MEC 或 CCL28）与 CCR3 和 CCR10 结合，并募集黏膜固有层中的 IgA 分泌浆细胞（IgA-ASC）。在使用 HIV-1(IIIB)病毒样颗粒（VLPs）的小鼠免疫模型中，评估了这种趋化因子增强 IgA-ASC 向黏膜部位迁移的能力。接受单独的 HIV-1(IIIB)VLPs、单独的 CCL28 或不相关的 CCL19 趋化因子的小鼠用作对照。结果显示，HIV-1(IIIB)VLP-CCL28 处理的小鼠的 CD19(+)脾细胞上 CCR3 和 CCR10 的表达显著增加。HIV-1 Env 特异性 IFN-γ、IL-4 和 IL-5 产生、总 IgA、抗 Env IgA 以及胃肠道黏膜 IgA 分泌浆细胞也显著增加。值得注意的是，来自 HIV-1(IIIB)VLP-CCL28 处理的小鼠的血清和阴道分泌物显示出对 HIV-1/B 亚型实验室株和异源 HIV-1/C 亚型原发性分离株的增强的中和活性。这些数据表明，CCL28 可用于增强可能在预防性 HIV 疫苗中发挥关键作用的 IgA 免疫反应。
