Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Mucosal Immunol. 2013 Jan;6(1):93-103. doi: 10.1038/mi.2012.52. Epub 2012 Jul 4.
An HIV-1 vaccine must elicit a clonally diverse virus-specific CD8+ T-cell response to contain mutant virus forms, and these responses must be present in mucosal tissues, which are the site of early HIV-1 replication. We show that systemic delivery of prototype vaccine vectors in rhesus monkeys induced SIV (simian immunodeficiency virus)-specific CD8+ T-cell responses in systemic and mucosal compartments with comparable clonal compositions. Although clonal sharing was maintained between the peripheral blood and lungs, the clonal constituents of the vaccine-induced CD8+ T-cell populations in the gastrointestinal mucosal tissues evolved away from the peripheral blood population. A phenotypic characterization indicated that the divergence was a consequence of differential trafficking and retention of the vaccine-induced cells in mucosal compartments. These findings highlight the circulation of vaccine-induced CD8+ T-cell populations between systemic and mucosal compartments and the importance of the expression of specific homing molecules for localization in mucosal tissues.
一种 HIV-1 疫苗必须能够引发克隆多样性的病毒特异性 CD8+ T 细胞反应，以遏制突变病毒形式，并且这些反应必须存在于黏膜组织中，因为黏膜组织是 HIV-1 早期复制的部位。我们表明，在恒河猴中系统递送原型疫苗载体可诱导 SIV（猴免疫缺陷病毒）特异性 CD8+ T 细胞反应，这些反应存在于全身和黏膜隔室中，且克隆组成具有可比性。尽管外周血和肺部之间存在克隆共享，但胃肠道黏膜组织中疫苗诱导的 CD8+ T 细胞群体的克隆成分逐渐偏离外周血群体。表型特征表明，这种差异是由于疫苗诱导的细胞在黏膜隔室中的不同运输和保留所致。这些发现强调了疫苗诱导的 CD8+ T 细胞群体在全身和黏膜隔室之间的循环，以及表达特定归巢分子对于定位在黏膜组织中的重要性。
