Abstract：
The skin at the site of HSV-2 reactivation is enriched for HSV-2-specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells, we studied skin biopsies and HSV-2-reactive CD4+ T cells from PBMCs by T cell receptor (TCR) β chain (TRB) sequencing before and after vaccination with a replication-incompetent whole-virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ TRB sequences from PBMCs in the skin TRB repertoire increased after the first vaccine dose. We found sustained expansion after vaccination of unique, skin-based T cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. In one participant, a switch in immunodominance occurred with the emergence of a TCR αβ pair after vaccination that was not detected in blood. This TCRαβ was shown to be HSV-2 reactive by expression of a synthetic TCR in a Jurkat-based NR4A1 reporter system. The skin in areas of HSV-2 reactivation possessed an oligoclonal TRB repertoire that was distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.
摘要：
HSV-2再活化位点处的皮肤富含HSV-2特异性T细胞。为了评估免疫治疗疫苗是否可以引发基于皮肤的记忆T细胞，我们通过T细胞受体(TCR)β链(TRB)测序研究了在接种无复制能力的全病毒HSV-2候选疫苗(HSV529)之前和之后的皮肤活检和来自PBMC的HSV-2反应性CD4+T细胞.在第一疫苗剂量后,皮肤TRB库中来自PBMC的HSV-2反应性CD4+TRB序列的表示增加。我们发现疫苗接种后的持续扩张是独一无二的，在从PBMC分离的HSV-2反应性CD4+T细胞中未检测到的皮肤型T细胞克隆型。在一个参与者中，免疫优势的转换发生在疫苗接种后TCRαβ对的出现,但在血液中未检测到.通过在基于Jurkat的NR4A1报告系统中表达合成TCR,显示该TCRαβ具有HSV-2反应性。HSV-2再激活区域的皮肤具有与循环不同的寡克隆TRB库。定义治疗性疫苗接种对HSV-2特异性TRB库的影响需要基于组织的评估。
