Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models
Liyen Loh,
Salomé Carcy,
Harsha S. Krovi,
Joanne Domenico,
Andrea Spengler,
Yong Lin,
Joshua Torres,
Rishvanth K. Prabakar,
William Palmer,
Paul J. Norman,
Matthew Stone,
Tonya Brunetti,
Hannah V. Meyer,
Laurent Gapin
Affiliations
Liyen Loh
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Salomé Carcy
School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
Harsha S. Krovi
Brigham and Women’s Hospital, Boston, MA, USA
Joanne Domenico
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Andrea Spengler
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Yong Lin
Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
Joshua Torres
Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
Rishvanth K. Prabakar
Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
William Palmer
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Paul J. Norman
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Matthew Stone
Children’s Hospital Colorado, Aurora, CO, USA
Tonya Brunetti
University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Hannah V. Meyer
Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; Corresponding author
Laurent Gapin
University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Corresponding author
Summary: The “innate-like” T cell compartment, known as Tinn, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity. We explore the transcriptional landscape of Tinn compared to conventional T cells (Tconv) in the human thymus and blood using single-cell RNA sequencing (scRNA-seq) and flow cytometry. In human blood, the majority of Tinn cells share an effector program driven by specific transcription factors, distinct from those governing Tconv cells. Conversely, only a fraction of thymic Tinn cells displays an effector phenotype, while others share transcriptional features with developing Tconv cells, indicating potential divergent developmental pathways. Unlike the mouse, human Tinn cells do not differentiate into multiple effector subsets but develop a mixed type 1/type 17 effector potential. Cross-species analysis uncovers species-specific distinctions, including the absence of type 2 Tinn cells in humans, which implies distinct immune regulatory mechanisms across species.
