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

Daniel Y. Hu, Rushika C Wirasinha, Christopher C. Goodnow, Stephen R Daley

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1007-1016
Number of pages10
JournalCell Death and Differentiation
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 2017

Cite this

Hu, Daniel Y. ; Wirasinha, Rushika C ; Goodnow, Christopher C. ; Daley, Stephen R. / IL-2 prevents deletion of developing T-regulatory cells in the thymus. In: Cell Death and Differentiation. 2017 ; Vol. 24, No. 6. pp. 1007-1016.
@article{e0cc620481c54af88da180e5957eb3ef,
title = "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.",
author = "Hu, {Daniel Y.} and Wirasinha, {Rushika C} and Goodnow, {Christopher C.} and Daley, {Stephen R}",
year = "2017",
month = "6",
doi = "10.1038/cdd.2017.38",
language = "English",
volume = "24",
pages = "1007--1016",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "6",

}

IL-2 prevents deletion of developing T-regulatory cells in the thymus. / Hu, Daniel Y.; Wirasinha, Rushika C; Goodnow, Christopher C.; Daley, Stephen R.

In: Cell Death and Differentiation, Vol. 24, No. 6, 06.2017, p. 1007-1016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - IL-2 prevents deletion of developing T-regulatory cells in the thymus

AU - Hu, Daniel Y.

AU - Wirasinha, Rushika C

AU - Goodnow, Christopher C.

AU - Daley, Stephen R

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016630505&partnerID=8YFLogxK

U2 - 10.1038/cdd.2017.38

DO - 10.1038/cdd.2017.38

M3 - Article

VL - 24

SP - 1007

EP - 1016

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 6

ER -