Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
J Immunol. 2018 May 1;200(9):3283-3290. doi: 10.4049/jimmunol.1800118. Epub 2018 Mar 30.
In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently -infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6CXCR3CCR4) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62LGPA33 Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells.
在传染病学领域，细胞群体转录组学对于深入了解保护性免疫反应非常有用，而传统的全血方法无法实现这一点。在这项研究中，我们应用了一种细胞群体转录组学策略来对记忆性 CD4 T 细胞进行分类，以确定潜伏性结核感染（LTBI）的新型免疫特征，并深入了解结核特异性 CD4 T 细胞的表型。我们发现了一个由 74 个基因组成的特征性基因签名，可将来自潜伏性感染健康受试者和未感染者的记忆性 CD4 T 细胞区分开来。该基因签名与 Th1*（CCR6CXCR3CCR4）亚群的 CD4 T 细胞的基因签名显著重叠，Th1亚群包含了大部分的结核特异性反应性，并且在 LTBI 中得到了扩展。特别是，三个 Th1基因（ABCB1、c-KIT 和 GPA33）在 LTBI 受试者的记忆性 CD4 T 细胞中，在 RNA 和蛋白水平上的表达与对照组相比存在差异。74 个基因签名还突出了新的表型标志物，进一步定义了包含结核特异性的 CD4 T 细胞亚群。我们发现大多数结核特异性表位反应性存在于 CD62LGPA33 Th1*亚群中。因此，通过结合细胞群体转录组学和单细胞蛋白谱分析技术，我们确定了 LTBI 的 CD4 T 细胞免疫特征，为结核特异性 CD4 T 细胞的表型提供了新的见解。
