Abstract
IL-2 contributes to the production, function, and homeostasis of CD4 +CD25+ Treg cells. However, it remains uncertain whether IL-2 is essential for the development of Treg cells in the thymus, their homeostasis in the periphery, or both. The present study was undertaken to investigate the contribution of IL-2 during thymic T reg cell development and its maintenance in peripheral immune tissue. Relying on genetic mouse models where IL-2R signaling was either completely blocked or selectively inhibited in peripheral CD4+CD25+ Treg cells, we show that the IL-2/IL-2R interaction is active in the thymus at the earliest stage of the development of Treg cells to promote their expansion and to up-regulate Foxp3 and CD25 to normal levels. Furthermore, CD4+CD25+Foxp3+ Treg cells with impaired IL-2-induced signaling persist in the periphery and control autoimmunity without constant thymic output. These peripheral Treg cells with poor responsiveness to IL-2 exhibited slower growth and extended survival in vivo, somewhat lower suppressive activity, and poor IL-2-dependent survival in vitro. Mixed thymic and bone marrow chimeric mice showed that wild-type-derived Treg cells were substantially more effective in populating peripheral immune tissue than Treg cells with impaired IL-2 signaling. Collectively, these data support the notion that normally IL-2 is a dominant mechanism controlling the number of thymic and peripheral T reg cells.
| Original language | English |
|---|---|
| Pages (from-to) | 4062-4071 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 178 |
| Issue number | 7 |
| State | Published - Apr 1 2007 |
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ASJC Scopus subject areas
- Immunology
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Function of the IL-2R for thymic and peripheral CD4+CD25 + Foxp3+ T regulatory cells. / Bayer, Allison L; Yu, Aixin; Malek, Thomas.
In: Journal of Immunology, Vol. 178, No. 7, 01.04.2007, p. 4062-4071.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Function of the IL-2R for thymic and peripheral CD4+CD25 + Foxp3+ T regulatory cells
AU - Bayer, Allison L
AU - Yu, Aixin
AU - Malek, Thomas
PY - 2007/4/1
Y1 - 2007/4/1
N2 - IL-2 contributes to the production, function, and homeostasis of CD4 +CD25+ Treg cells. However, it remains uncertain whether IL-2 is essential for the development of Treg cells in the thymus, their homeostasis in the periphery, or both. The present study was undertaken to investigate the contribution of IL-2 during thymic T reg cell development and its maintenance in peripheral immune tissue. Relying on genetic mouse models where IL-2R signaling was either completely blocked or selectively inhibited in peripheral CD4+CD25+ Treg cells, we show that the IL-2/IL-2R interaction is active in the thymus at the earliest stage of the development of Treg cells to promote their expansion and to up-regulate Foxp3 and CD25 to normal levels. Furthermore, CD4+CD25+Foxp3+ Treg cells with impaired IL-2-induced signaling persist in the periphery and control autoimmunity without constant thymic output. These peripheral Treg cells with poor responsiveness to IL-2 exhibited slower growth and extended survival in vivo, somewhat lower suppressive activity, and poor IL-2-dependent survival in vitro. Mixed thymic and bone marrow chimeric mice showed that wild-type-derived Treg cells were substantially more effective in populating peripheral immune tissue than Treg cells with impaired IL-2 signaling. Collectively, these data support the notion that normally IL-2 is a dominant mechanism controlling the number of thymic and peripheral T reg cells.
AB - IL-2 contributes to the production, function, and homeostasis of CD4 +CD25+ Treg cells. However, it remains uncertain whether IL-2 is essential for the development of Treg cells in the thymus, their homeostasis in the periphery, or both. The present study was undertaken to investigate the contribution of IL-2 during thymic T reg cell development and its maintenance in peripheral immune tissue. Relying on genetic mouse models where IL-2R signaling was either completely blocked or selectively inhibited in peripheral CD4+CD25+ Treg cells, we show that the IL-2/IL-2R interaction is active in the thymus at the earliest stage of the development of Treg cells to promote their expansion and to up-regulate Foxp3 and CD25 to normal levels. Furthermore, CD4+CD25+Foxp3+ Treg cells with impaired IL-2-induced signaling persist in the periphery and control autoimmunity without constant thymic output. These peripheral Treg cells with poor responsiveness to IL-2 exhibited slower growth and extended survival in vivo, somewhat lower suppressive activity, and poor IL-2-dependent survival in vitro. Mixed thymic and bone marrow chimeric mice showed that wild-type-derived Treg cells were substantially more effective in populating peripheral immune tissue than Treg cells with impaired IL-2 signaling. Collectively, these data support the notion that normally IL-2 is a dominant mechanism controlling the number of thymic and peripheral T reg cells.
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UR - http://www.scopus.com/inward/citedby.url?scp=33947667310&partnerID=8YFLogxK
M3 - Article
C2 - 17371960
AN - SCOPUS:33947667310
VL - 178
SP - 4062
EP - 4071
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -