記憶樣HCV特異性CD8+ T細胞可長期保留HCV的感染印記
作者：
小柯機器人發布時間：2021/1/5 16:23:30
慢性C型肝炎病毒（HCV）感染治癒後，記憶樣HCV特異性CD8+ T細胞仍保留其分子印記，這一成果由德國弗萊堡大學附屬醫院Maike Hofmann和Robert Thimme團隊經過不懈努力而取得。 該研究於2021年1月4日發表於國際學術期刊《自然-免疫學》。
研究人員通過中間集探究了記憶樣和終末耗竭HCV特異性CD8+ T細胞之間的祖先-後代關係。單細胞轉錄組學表明，在利用直接抗病毒（DAA）治療治癒後，記憶樣細胞得以維持，終末耗竭細胞丟失，從而導致整體HCV特異性CD8+ T細胞反應的記憶極化。
然而，仍然可以檢測到記憶樣CD8+ T細胞耗竭的核心特徵或靶向變體表位的HCV特異性CD8+ T細胞。這些結果確定了即使在停止長期抗原刺激後，HCV特異性CD8+ T細胞中仍長期保留T細胞耗竭的分子標誌。
據了解，在慢性HCV感染中，耗竭HCV特異性CD8+ T細胞由記憶樣和終末分化的子集構成。但是，對通過DAA治療消除慢性抗原刺激後，對這兩個子集的分子概況和細胞命運仍知之甚少。
附：英文原文
Title: Memory-like HCV-specific CD8 + T cells retain a molecular scar after cure of chronic HCV infection
Author: Nina Hensel, Zuguang Gu, Sagar, Dominik Wieland, Katharina Jechow, Janine Kemming, Sian Llewellyn-Lacey, Emma Gostick, Oezlem Sogukpinar, Florian Emmerich, David A. Price, Bertram Bengsch, Tobias Boettler, Christoph Neumann-Haefelin, Roland Eils, Christian Conrad, Ralf Bartenschlager, Dominic Grn, Naveed Ishaque, Robert Thimme, Maike Hofmann
Issue&Volume: 2021-01-04
Abstract: In chronic hepatitis C virus (HCV) infection, exhausted HCV-specific CD8+ T cells comprise memory-like and terminally exhausted subsets. However, little is known about the molecular profile and fate of these two subsets after the elimination of chronic antigen stimulation by direct-acting antiviral (DAA) therapy. Here, we report a progenitor–progeny relationship between memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate subset. Single-cell transcriptomics implicated that memory-like cells are maintained and terminally exhausted cells are lost after DAA-mediated cure, resulting in a memory polarization of the overall HCV-specific CD8+ T cell response. However, an exhausted core signature of memory-like CD8+ T cells was still detectable, including, to a smaller extent, in HCV-specific CD8+ T cells targeting variant epitopes. These results identify a molecular signature of T cell exhaustion that is maintained as a chronic scar in HCV-specific CD8+ T cells even after the cessation of chronic antigen stimulation.
DOI: 10.1038/s41590-020-00817-w
Source: https://www.nature.com/articles/s41590-020-00817-w