PT Journal
AU Lukyanov, DK
   Kriukova, VV
   Ladell, K
   Shagina, IA
   Staroverov, DB
   Minasian, BE
   Fedosova, AS
   Shelyakin, P
   Suchalko, ON
   Komkov, AY
   Blagodatskikh, KA
   Miners, KL
   Britanova, OV
   Franke, A
   Price, DA
   Chudakov, DM
TI Repertoire-based mapping and time-tracking of T helper cell subsets in scRNA-Seq
SO Frontiers in immunology
JI Front. Immunol.
PY 2025
BP 1536302
VL 16
PU Frontiers Media SA
DI 10.3389/fimmu.2025.1536302
WP https://macau.uni-kiel.de/receive/macau_mods_00005883
LA en
DE T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer; Humans; Sequence Analysis, RNA; Single-Cell Analysis; RNA-Seq; Single-Cell Gene Expression Analysis; T cell memory; helper T cell subsets; Th17; Th22; Scrna-seq; Immune Repertoires; Sctcr-seq; Cytotoxic Cd4+ T Cells
SN 1664-3224
AB This approach accurately positions the Th1, Th1-17, Th17, Th22, Th2a, Th2, T follicular helper (Tfh), and regulatory T-cell (Treg) subsets, outperforming mapping based on CITE-Seq. Remarkably, the mapping is tightly focused on specific scRNA-Seq clusters, despite 4-year interval between subset sorting and the effector CD4+ scRNA-Seq experiment. These findings highlight the intrinsic program stability of Th clones circulating in peripheral blood. Repertoire overlap analysis at the scRNA-Seq level confirms that the circulating Th1, Th2, Th2a, Th17, Th22, and Treg subsets are clonally independent. However, a significant clonal overlap between the Th1 and cytotoxic CD4+ T-cell clusters suggests that cytotoxic CD4+ T cells differentiate from Th1 clones. In addition, this study resolves a longstanding ambiguity: we demonstrate that, while CCR10+ Th cells align with a specific Th22 scRNA-Seq cluster, CCR10-CCR6+CXCR3-CCR4+ cells, typically classified as Th17, represent a mixture of bona fide Th17 cells and clonally unrelated CCR10low Th22 cells. The clear distinction between the Th17 and Th22 subsets should influence the development of vaccine- and T-cell-based therapies. Furthermore, we show that severe acute SARS-CoV-2 infection induces systemic type 1 interferon (IFN) activation of naive Th cells. An increased proportion of effector IFN-induced Th cells is associated with a moderate course of the disease but remains low in critical COVID-19 cases. Using integrated scRNA-Seq, TCR-Track, and CITE-Seq data from 122 donors, we provide a comprehensive Th scRNA-Seq reference that should facilitate further investigation of Th subsets in fundamental and clinical studies.
PI Lausanne
ER