Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037.
Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093.
Immunohorizons. 2020 Jun 4;4(6):292-307. doi: 10.4049/immunohorizons.2000031.
CD8 T cells are considered important contributors to the immune response against , yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell-specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8Vα7.2CD161 MAITs: MR1 tetramer and MR1 tetramer, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected individuals did not reveal significant differences for MR1 tetramer MAITs. However, gene expression of MR1 tetramer MAITs showed large interindividual diversity and a tuberculosis-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer cells as compared with MR1 tetramer Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer MAITs as well as a difference in phenotype in the rare population of MR1 tetramer MAITs compared with uninfected controls.
CD8 T 细胞被认为是针对 的免疫反应的重要贡献者，但目前对于它们的特定免疫特征和表型知之甚少。在这项研究中，我们应用了细胞群体转录组学策略来定义人类潜伏性结核感染（LTBI）记忆 CD8 T 细胞的免疫特征。我们发现了一个 41 个基因的特征，可以区分来自健康 LTBI 受试者和未感染者的记忆 CD8 T 细胞。该基因特征主要由与黏膜相关不变 T 细胞（MAITs）相关的基因主导，反映了 LTBI 个体中 MAITs 的频率较低。在两个队列之间没有证据表明存在常规 CD8 T 细胞特异性特征。因此，我们根据 Vα7.2 和 CD161 的表达以及与 MHC 相关蛋白 1（MR1）四聚体的染色，更详细地研究了 MAITs。这揭示了两种不同的 CD8Vα7.2CD161 MAIT 细胞群：MR1 四聚体和 MR1 四聚体，它们与记忆 CD8 T 细胞相比具有独特的基因表达。LTBI 与未感染者的转录组分析未显示 MR1 四聚体 MAITs 的显著差异。然而，MR1 四聚体 MAITs 的基因表达显示出较大的个体间多样性和结核特异性特征。与 MR1 四聚体相比，MR1 四聚体细胞的 TCR-α 和 -β 受体库更加多样化，进一步加强了这一点。因此，与未感染者相比，潜伏性结核受试者的循环记忆 CD8 T 细胞中常规的 MR1 四聚体 MAITs 数量减少，并且罕见的 MR1 四聚体 MAITs 表型也存在差异。
