One naive T cell, multiple fates in CD8+ T cell differentiation

Author:

Gerlach Carmen1,van Heijst Jeroen W.J.1,Swart Erwin1,Sie Daoud1,Armstrong Nicola1,Kerkhoven Ron M.1,Zehn Dietmar2,Bevan Michael J.3,Schepers Koen1,Schumacher Ton N.M.1

Affiliation:

1. Division of Immunology, Central Microarray Facility, and Bioinformatics and Statistics Group, Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

2. Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland

3. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

Abstract

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR–pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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