pDCs amplify tissue-resident memory CD8+ T cell responses during viral reinfection.

Published in: J Exp Med 2026 Feb; 223(2):

Authors: Hernández-García E, Galán M, Khouili SC, Moya-Ruiz E, Redondo-Urzainqui A, Cueto FJ, Martínez-Cano S, Rodrigo-Tapias M, Tomasello E, Mañes S, Dalod M, Sancho D, Iborra S

Summary

Resident memory CD8+ T cells (Trms) are essential for protecting barrier nonlymphoid tissues (NLTs) against reinfection, yet the involvement of dendritic cells (DCs) in this process and the nature of Trm-DC interactions within these tissues remain poorly understood. Our study demonstrates that upon reactivation, memory CD8+ T cells located in the skin-independently of circulating memory counterparts-initiate the infiltration and maturation of plasmacytoid DCs (pDCs) in the tissue. This, in turn, promotes the maturation of conventional type 1 DCs (cDC1s) through type I IFN (IFN-I) signaling in a pDC-dependent manner. Depletion of pDCs or blocking IFN-I signaling disrupts this axis, severely impairing Trm-driven protection against secondary infections with vaccinia virus (VACV) in the skin. Notably, this pDC-dependent, IFN-I-mediated pathway is also essential for Trm-mediated protection against secondary respiratory infections with influenza A virus (IAV). Our findings uncover a crucial collaboration between Trm, pDCs, and cDC1s, offering new insights for enhancing vaccines.

Link to Pubmed [PMID] – 41288524

Link to DOI – 10.1084/jem.20250099