Two subsets of stem-like CD8(+) memory T cell progenitors with distinct fate commitments in humans.
Two subsets of stem-like CD8(+) memory T cell progenitors with distinct fate commitments in humans.
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DOI：
10.1038/s41590-020-0791-5
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发表时间：
2020-12
影响因子：
30.5
通讯作者：
Lugli E
中科院分区：
文献类型：
--
作者：
Galletti G;De Simone G;Mazza EMC;Puccio S;Mezzanotte C;Bi TM;Davydov AN;Metsger M;Scamardella E;Alvisi G;De Paoli F;Zanon V;Scarpa A;Camisa B;Colombo FS;Anselmo A;Peano C;Polletti S;Mavilio D;Gattinoni L;Boi SK;Youngblood BA;Jones RE;Baird DM;Gostick E;Llewellyn-Lacey S;Ladell K;Price DA;Chudakov DM;Newell EW;Casucci M;Lugli E
T细胞记忆依赖于具有干细胞样特性的抗原特异性祖细胞的产生。然而，这些祖细胞的身份仍然不清楚，排除了对支持抗原经历的T细胞异质性的分化轨迹的充分理解。我们使用了一种由单细胞RNA测序数据指导的系统方法来绘制生理条件下人类CD 8+记忆T细胞库的组织结构。我们确定了两个以前未被识别的克隆，表观遗传，功能，表型和转录不同的干细胞样CD 8+记忆T细胞的子集。缺乏抑制性受体程序性死亡-1（PD-1）和具有IG和ITIM结构域的T细胞免疫受体（TIGIT）的祖细胞被定型为功能性谱系，而表达PD-1和TIGIT的祖细胞被定型为功能失调的衰竭样谱系。总的来说，这些数据揭示了人类CD 8+记忆T细胞库中存在平行分化程序，这对免疫疗法和疫苗的开发具有潜在的广泛意义。
T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically, and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data revealed the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.
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影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
11.4
作者：
Giordano, Marilyn;Henin, Coralie;Verdeil, Gregory
通讯作者：
Verdeil, Gregory