A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool

The Journal of Experimental Medicine, vol. 217

Abstract

An increasing body of evidence emphasizes the role of tissue-resident memory T cells (TRM) in the defense against recurring pathogens and malignant neoplasms. However, little is known with regard to the origin of these cells and their kinship to other CD8+ T cell compartments. To address this issue, we followed the antigen-specific progeny of individual naive CD8+ T cells to the T effector (TEFF), T circulating memory (TCIRCM), and TRM pools by lineage-tracing and single-cell transcriptome analysis. We demonstrate that a subset of T cell clones possesses a heightened capacity to form TRM, and that enriched expression of TRM-fate-associated genes is already apparent in the circulating TEFF offspring of such clones. In addition, we demonstrate that the capacity to generate TRM is permanently imprinted at the clonal level, before skin entry. Collectively, these data provide compelling evidence for early stage TRM fate decisions and the existence of committed TRM precursor cells in the circulatory TEFF compartment.

Authors 9

1. Lianne Kok

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

2. Feline E. Dijkgraaf

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

3. Jos H. M. Urbanus

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

4. Kaspar Bresser

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

5. David W. Vredevoogd

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

6. Rebeca F. Cardoso

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1

7. Leïla Perié

   Centre National de la Recherche Scientifique · Université Paris Sciences et Lettres · Physique des Cellules et Cancers · Institut Curie

   Affiliation as printed

   Institut Curie, Université Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR168, Paris, France 2

8. Joost B. Beltman Aachen Division of Drug Discovery and Safety Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Drug Discovery & Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands 3

9. Ton N. Schumacher corresponding Aachen Department of Immunohematology and Blood Transfusion

   Leiden University Medical Center · The Netherlands Cancer Institute

   Affiliation as printed

   Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands 4

   Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands 1