A fetal wave of human type 3 effector gamma delta cells with restricted TCR diversity persists into adulthood
| Autor: | Reinhold Förster, Bowen Zhang, Alina Borchers, Ulf Panzer, Constantin von Kaisenberg, Christian Koenecke, Christian Schultze-Florey, Immo Prinz, Anja Bubke, Elena Bruni, Yang Li, Alina Suzann Fichtner, Xiaojing Chu, Inga Sandrock, Likai Tan, Ansgar Schulz, Sarina Ravens, Ivan Odak, Michael Jarek, Christian Krebs |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male SUBSETS T cell Immunology C-C chemokine receptor type 6 UNIQUE Biology Lymphocyte Activation PHENOTYPE Fetal Development 03 medical and health sciences 0302 clinical medicine RAR-related orphan receptor gamma T-Lymphocyte Subsets MAPS medicine Humans RNA-Seq Intraepithelial Lymphocytes Cells Cultured Effector T-cell receptor Cell Differentiation Receptors Antigen T-Cell gamma-delta General Medicine EXPANSION Fetal Blood Phenotype Embryonic stem cell Cell biology KLRB1 030104 developmental biology medicine.anatomical_structure DIFFERENTIATION T-CELLS VISUALIZATION Female Single-Cell Analysis REQUIREMENTS 030215 immunology EXPRESS |
| Zdroj: | Science immunology, 6(58):0125. AMER ASSOC ADVANCEMENT SCIENCE |
| ISSN: | 2470-9468 |
| Popis: | Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector gamma delta 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 gamma delta T cells. Here, we present a protocol for high-throughput sequencing of TRG and TRD pairs that comprise the clonal gamma delta TCR. In combination with single-cell RNA sequencing, multiparameter flow cytometry, and TCR sequencing, we reveal a high heterogeneity of gamma delta T cells sorted from neonatal and adult blood that correlated with TCR usage. Immature gamma delta T cell clusters displayed mixed and diverse TCRs, but effector cell types segregated according to the expression of either highly expanded individual V delta 1(+) TCRs or moderately expanded semi-invariant V gamma 9V delta 2(+) TCRs. The V gamma 9V delta 2(+) 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 V gamma 9V delta 2(+) 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 gamma delta 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 gamma delta T cells with semi-invariant V gamma 9V delta 2(+) TCR develop in the early fetal thymus and persist into adulthood. |
| Databáze: | OpenAIRE |
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