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Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.

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Τίτλος: Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.
Συγγραφείς: Sajiki Y; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Ando S; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Perkins CM; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Huang YC; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Immunology Graduate Program, University of Cincinnati College of Medicine , Cincinnati, OH, USA., Smith KE; Comparative Medicine Division, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Doerning CM; Comparative Medicine Division, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Hildeman DA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Araki K; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Πηγή: The Journal of experimental medicine [J Exp Med] 2026 Oct 05; Vol. 223 (10). Date of Electronic Publication: 2026 Aug 31.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, NY : Rockefeller University Press
Ιατρικοί όροι (MeSH): CD8-Positive T-Lymphocytes*/immunology , Memory T Cells*/immunology , T-Lymphocyte Subsets*/immunology , Cell Plasticity*/immunology , Immunologic Memory*, Antigens, Ly/immunology ; Antigens, Ly/metabolism ; Receptors, CXCR3/immunology ; Animals ; Mice ; Mice, Inbred C57BL ; Signal Transduction
Περίληψη: While significant progress has been made in defining subsets among antigen-experienced CD8 T cells, the heterogeneity of naïve CD8 T cells remains poorly understood. Here, we identify naïve CD8 T cell subsets with superior persistence and an enhanced capacity to generate effector and memory cells, leading to more effective protection. These functionally superior naïve CD8 T cells are marked by IL-18Rα, CD73, and CXCR3, and functionally less potent naïve CD8 T cells can convert into these superior subsets through tonic TCR signaling. Their enhanced response to infections is driven by better survival of the progeny effector cells during the T cell expansion phase. This improved survival is mediated by increased Ly6C expression on effector cells derived from these functionally superior naïve cells. Collectively, our findings reveal functional heterogeneity and plasticity among naïve CD8 T cells and uncover a mechanism by which functionally superior naïve subsets drive robust CD8 T cell responses, providing a previously unrecognized layer of immune regulation.
(© 2026 Sajiki et al.)
Σχόλια: Update of: bioRxiv. 2025 Oct 17:2025.10.16.682909. doi: 10.1101/2025.10.16.682909.. (PMID: 41279312)
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Grant Information: R01AI139675 United States NH NIH HHS; Cincinnati Children's Hospital Research Foundation; R01AI184466 United States NH NIH HHS; R01 AI139675 United States AI NIAID NIH HHS; 202260075 Japan Society for the Promotion of Science; T32AI165396 United States NH NIH HHS; T32 AI165396 United States AI NIAID NIH HHS; R01 AI184466 United States AI NIAID NIH HHS
Substance Nomenclature: 0 (Antigens, Ly)
0 (Ly-6C antigen, mouse)
0 (Receptors, CXCR3)
Entry Date(s): Date Created: 20260831 Date Completed: 20260831 Latest Revision: 20260908
Update Code: 20260908
PubMed Central ID: PMC13540382
DOI: 10.1084/jem.20252076
PMID: 42671388
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1540-9538
DOI:10.1084/jem.20252076