Transcription factor expression profiling to characterize differentiation of antigen-specific CD8 T cells induced by a live attenuated viral vaccine. (113.18)
Transcription factor expression profiling to characterize differentiation of antigen-specific CD8 T cells induced by a live attenuated viral vaccine. (113.18)
复制标题
转录因子表达谱分析可表征减毒活病毒疫苗诱导的抗原特异性 CD8 T 细胞的分化。
作者：
J. Billingsley;P. Rajakumar;Nadine C. Salisch;Y. Kuzmichev;H. Hong;M. Connole;R. K. Reeves;R. Johnson
减毒活SIV （SIVΔnef）是在猕猴中诱导对致病性SIV攻击的保护最有效的方法。部分由CD8 T细胞反应介导的保护性免疫与siv特异性T细胞的表型成熟相关，但仍未完全了解。T细胞转录因子（TF）的表达谱分析为表征抗原特异性T细胞分化提供了一种新的方法。使用高度平行的qRT-PCR来表征21 TF在naïve、中枢、过渡性和效应记忆T细胞亚群中的表达，以及在SIVΔnef接种疫苗后保护程度较低（第5周）和保护程度较高（第20周）的siv特异性CD8 T细胞中的表达。无监督聚类将CD4和CD8 T细胞样本组织成与细胞表面表型一致的组。TF在siv特异性CD8+ T细胞中按时间分离，第20周细胞表现出TF的表达增加，这与维持沉默（TCF7， BAZF）和促进效应功能（Eomes, T- bet）有关。在不同SIV表位特异性的T细胞中观察到不同的表达谱，这与不同的表位逃逸动力学一致。TF表达谱表明，与保护相关的T细胞反应可能包括记忆细胞和效应细胞的特征。TF表达谱可以为基于经典表型标记的记忆细胞分化分析提供数据补充。
Live attenuated SIV (SIVΔnef) is the most effective approach to induce protection to pathogenic SIV challenge in macaques. Protective immunity, in part mediated by CD8 T cell responses, correlates with phenotypic maturation of SIV-specific T cells, but remains incompletely understood. Expression profiling of T cell transcription factors (TF) offers a novel approach to characterize antigen-specific T cell differentiation. Highly parallel qRT-PCR was used to characterize the expression of 21 TF in naïve, central, transitional, and effector memory T cell subsets, and in SIV-specific CD8 T cells obtained at times associated with lesser protection (wk 5) and greater protection (wk 20) following SIVΔnef vaccination. Unsupervised clustering organized samples from CD4 and CD8 T cells into groups concordant with cell surface phenotype. TF expression in SIV-specific CD8+ T cells segregated by time, with wk 20 cells exhibiting increased expression of TF associated with both maintenance of quiescence (TCF7, BAZF) and promotion of effector function (Eomes, T-Bet). Different expression profiles were observed in T cells specific for different SIV epitopes, consistent with different epitope escape kinetics. TF expression profiling suggests T cell responses correlated with protection may include characteristics of both memory and effector cells. TF expression profiling can provide data complementary to the analysis of memory cell differentiation based on classical phenotypic markers.