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 language | English |
|---|---|
| Pages (from-to) | 1007-1016 |
| Number of pages | 10 |
| Journal | Cell Death and Differentiation |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2017 |
Cite this
}
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 journal › Article › Research › peer-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 -