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

Carmen Gerlach, Jeroen W J van Heijst, Erwin Swart, Daoud Sie, Nicola Armstrong, Ron M Kerkhoven, Dietmar Zehn, Michael J Bevan, Koen Schepers, Ton N M Schumacher

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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.

Original languageEnglish
Pages (from-to)1235-46
Number of pages12
JournalJournal of Experimental Medicine
Issue number6
Publication statusPublished - 7 Jun 2010

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