生物
效应器
T细胞受体
细胞生物学
先天免疫系统
T细胞
流式细胞术
免疫学
免疫系统
作者
Likai Tan,Alina Suzann Fichtner,Elena Bruni,Ivan Odak,Inga Sandrock,Anja Bubke,Alina Borchers,Christian Schultze-Florey,Christian Koenecke,Reinhold Förster,Michael Jarek,Constantin von Kaisenberg,Ansgar Schulz,Xiaojing Chu,Bowen Zhang,Yang Li,Ulf Panzer,Christian Krebs,Sarina Ravens,Immo Prinz
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-02
卷期号:6 (58)
被引量:45
标识
DOI:10.1126/sciimmunol.abf0125
摘要
Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process occurs similarly in humans and whether it comprises a dedicated subset of innate-like type 3 effector γδ T cells. Here, we present a protocol for high-throughput sequencing of TRG and TRD pairs that comprise the clonal γδTCR. In combination with single-cell RNA sequencing, multiparameter flow cytometry, and TCR sequencing, we reveal a high heterogeneity of γδ T cells sorted from neonatal and adult blood that correlated with TCR usage. Immature γδ T cell clusters displayed mixed and diverse TCRs, but effector cell types segregated according to the expression of either highly expanded individual Vδ1+ TCRs or moderately expanded semi-invariant Vγ9Vδ2+ TCRs. The Vγ9Vδ2+ T cells shared expression of genes that mark innate-like T cells, including ZBTB16 (encoding PLZF), KLRB1, and KLRC1, but consisted of distinct clusters with unrelated Vγ9Vδ2+ TCR clones characterized either by TBX21, FCGR3A, and cytotoxicity-associated gene expression (type 1) or by CCR6, RORC, IL23R, and DPP4 expression (type 3). Effector γδ T cells with type 1 and type 3 innate T cell signatures were detected in a public dataset of early embryonic thymus organogenesis. Together, this study suggests that functionally distinct waves of human innate-like effector γδ T cells with semi-invariant Vγ9Vδ2+ TCR develop in the early fetal thymus and persist into adulthood.
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