Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
Institute for Research in Biomedicine, Bellinzona, Università della Svizzera Italiana, Lugano, Switzerland.
Science. 2015 Jan 23;347(6220):400-6. doi: 10.1126/science.1260668. Epub 2014 Dec 4.
Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.
不同类型的 CD4(+) T 细胞保护宿主免受不同类别的病原体侵害。然而,尚不清楚给定的病原体是否会诱导单一类型的极化 T 细胞。通过结合抗原刺激和 T 细胞受体深度测序,我们发现人类病原体和疫苗特异性辅助性 T 细胞 1(T(H)1)、T(H)2 和 T(H)17 记忆细胞具有不同的频率,但具有可比的多样性,不仅包括向单一命运极化的克隆,还包括其后代获得多种命运的克隆。体外由病原体初始的单个幼稚 T 细胞也可能产生多种命运。我们的结果揭示了人类 T 细胞反应中出乎意料的程度的克隆间和克隆内功能异质性,并表明极化反应是由优先扩增而不是初始引起的。