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IL-2 prevents deletion of developing T-regulatory cells in the thymus

Abstract

In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second.

Type Journal
ISBN 1476-5403 (Electronic) 1350-9047 (Linking)
Authors Hu, D. Y.; Wirasinha, R. C.; Goodnow, C. C.; Daley, S. R.
Responsible Garvan Author Prof Christopher Goodnow
Publisher Name CELL DEATH AND DIFFERENTIATION
Published Date 2017-06-30 00:00:00
Published Volume 24
Published Issue 6
Published Pages 1007-1016
Status Published in-print
DOI 10.1038/cdd.2017.38
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28362433