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Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses

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2020

Nat Immunol. 2020 Jul 13. doi: 10.1038/s41590-020-0723-4. Online ahead of print.

Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses

FM Behr;L Parga-Vidal;NAM Kragten;TJP van Dam;TH Wesselink;BS Sheridan;R Arens;RAW van Lier;R Stark;KPJM van Gisbergen

Department of Hematopoiesis & Department of Molecular and Cellular Hemostasis, Sanquin Research and Landsteiner Laboratory, and Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.

Service type: Knock-in mice

Abstract

Tissue-resident memory CD8+ T cells (TRM cells) are crucial in protecting against reinvading pathogens, but the impact of reinfection on their tissue confinement and contribution to recall responses is unclear. We developed a unique lineage tracer mouse model exploiting the TRM-defining transcription factor homolog of Blimp-1 in T cells (Hobit) to fate map the TRM progeny in secondary responses. After reinfection, a sizeable fraction of secondary memory T cells in the circulation developed downstream of TRM cells. These tissue-experienced ex-TRM cells shared phenotypic properties with the effector memory T cell population but were transcriptionally and functionally distinct from other secondary effector memory T cell cells. Adoptive transfer experiments of TRM cells corroborated their potential to form circulating effector and memory cells during recall responses. Moreover, specific ablation of primary TRM cell populations substantially impaired the secondary T cell response, both locally and systemically. Thus, TRM cells retain developmental plasticity and shape both local and systemic T cell responses on reinfection.

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