Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models
Liyen Loh, Salomé Carcy, S. Harsha Krovi, Joanne Domenico, Andrea Spengler, Yong Lin, Joshua Torres, Rishvanth K. Prabakar, William Palmer, Paul J. Norman, Matthew L. Stone, Tonya M. Brunetti, Hannah V. Meyer, Laurent Gapin
Abstract
The "innate-like" T cell compartment, known as T inn , represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity. We explore the transcriptional landscape of T inn compared to conventional T cells (T conv ) in the human thymus and blood using single-cell RNA sequencing (scRNA-seq) and flow cytometry. In human blood, the majority of T inn cells share an effector program driven by specific transcription factors, distinct from those governing T conv cells. Conversely, only a fraction of thymic T inn cells displays an effector phenotype, while others share transcriptional features with developing T conv cells, indicating potential divergent developmental pathways. Unlike the mouse, human T inn 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 T inn cells in humans, which implies distinct immune regulatory mechanisms across species.