Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models
The "innate-like" T cell compartment, known as T<sub>inn</sub>, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity. We explore the transcriptional landscape of T<sub>inn</sub> compared to conventional T cells (T<sub>conv</sub>) in the human thymus and blood using single-cell RNA sequencing (scRNA-seq) and flow cytometry. In human blood, the majority of T<sub>inn</sub> cells share an effector program driven by specific transcription factors, distinct from those governing T<sub>conv</sub> cells. Conversely, only a fraction of thymic T<sub>inn</sub> cells displays an effector phenotype, while others share transcriptional features with developing T<sub>conv</sub> cells, indicating potential divergent developmental pathways. Unlike the mouse, human T<sub>inn</sub> 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<sub>inn</sub> cells in humans, which implies distinct immune regulatory mechanisms across species.
Authors
- Matthew L. Stone
- Hannah V. Meyer (ORCID: https://orcid.org/0000-0003-4564-0899)
- Salomé Carcy (ORCID: https://orcid.org/0009-0009-2488-9418)
- Paul J. Norman (ORCID: https://orcid.org/0000-0001-8370-7703)
- Rishvanth K. Prabakar (ORCID: https://orcid.org/0000-0002-2377-1567)
- Laurent Gapin (ORCID: https://orcid.org/0000-0001-9730-5174)
- Tonya M. Brunetti (ORCID: https://orcid.org/0000-0002-2228-2198)
- Yong Lin
- Joanne Domenico
- Andrea Spengler
- Liyen Loh (ORCID: https://orcid.org/0000-0002-1676-0579)
- William Hunt Palmer (ORCID: https://orcid.org/0000-0002-0348-6339)
- Joshua Torres (ORCID: https://orcid.org/0009-0002-6240-2622)
- S. Harsha Krovi (ORCID: https://orcid.org/0000-0003-4661-617X)
Institutions
- Brigham and Women's Hospital (US)
- Cold Spring Harbor Laboratory (US)
- Children's Hospital Colorado (US)
- University of Colorado Anschutz Medical Campus (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114705
- Citations
- 14
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- National Science Foundation
- Colorado State University
- Cold Spring Harbor Laboratory
- Georgia Clinical and Translational Science Alliance
- Northwell Health
- National Institutes of Health
- Directorate for Biological Sciences
- University of Colorado Boulder
- Anschutz Medical Campus, University of Colorado
- Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory
- National Center for Advancing Translational Sciences