Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Biostatistics, Bioinformatics and Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; and.
J Immunol. 2022 Aug 1;209(3):526-534. doi: 10.4049/jimmunol.2101211. Epub 2022 Jul 8.
Ag-specific T cells play a critical role in responding to viral infections. In the RV144 HIV vaccine clinical trial, a rare subset of HIV-specific polyfunctional CD4 T cells correlated with reduced risk of HIV-1 infection. Polyfunctional T cells are a subset of Ag-specific T cells that are able to simultaneously produce multiple effector cytokines. Little is known about what differentiates polyfunctional T cells from other vaccine-elicited T cells in humans. Therefore, we developed a novel live-cell multiplexed cytokine capture assay to identify, isolate, and transcriptionally profile vaccine-specific polyfunctional CD4 T cells. We applied these methods to samples from subjects who received the RV144 vaccine regimen, as part of the HVTN 097 clinical trial. We identified two surface receptors (CD44 and CD82) upregulated on polyfunctional T cells and a Th2-biased transcriptional signature ( and ) that predicted the envelope-specific polyfunctional CD4 T cell profiles that had correlated with reduced risk of HIV infection in RV144. By linking single-cell transcriptional and functional profiles, we may be able to further define the potential contributions of polyfunctional T cells to effective vaccine-elicited immunity.
Ag 特异性 T 细胞在应对病毒感染中发挥着关键作用。在 RV144 HIV 疫苗临床试验中，与 HIV-1 感染风险降低相关的是 HIV 特异性多功能 CD4 T 细胞的罕见亚群。多功能 T 细胞是 Ag 特异性 T 细胞的一个亚群，能够同时产生多种效应细胞因子。目前尚不清楚多功能 T 细胞与人类中其他疫苗诱导的 T 细胞有何区别。因此，我们开发了一种新型的活细胞多重细胞因子捕获分析方法，用于鉴定、分离和转录分析疫苗特异性多功能 CD4 T 细胞。我们将这些方法应用于接受 RV144 疫苗方案的受试者样本中，作为 HVTN 097 临床试验的一部分。我们鉴定了两种在多功能 T 细胞上上调的表面受体（CD44 和 CD82）和一个偏向 Th2 的转录特征（和），该特征预测了与 RV144 中 HIV 感染风险降低相关的包膜特异性多功能 CD4 T 细胞特征。通过将单细胞转录和功能特征联系起来，我们也许能够进一步确定多功能 T 细胞对有效疫苗诱导免疫的潜在贡献。
