Projects per year
Abstract
A key role of the thymic medulla is to negatively select autoreactive CD4(+) and CD8(+) thymocytes, a process important for T cell tolerance induction. However, the involvement of the thymic medulla in other aspects of αβ T cell development, including the generation of Foxp3(+) natural regulatory T cells (nTreg cells) and the continued maturation of positively selected conventional αβ T cells, is unclear. We show that newly generated conventional CD69(+)Qa2(-) CD4 single-positive thymocytes mature to the late CD69(-)Qa2(+) stage in the absence of RelB-dependent medullary thymic epithelial cells (mTECs). Furthermore, an increasing ability to continue maturation extrathymically is observed within the CD69(+)CCR7(-/lo)CCR9(+) subset of conventional SP4 thymocytes, providing evidence for an independence from medullary support by the earliest stages after positive selection. In contrast, Foxp3(+) nTreg cell development is medullary dependent, with mTECs fostering the generation of Foxp3(-)CD25(+) nTreg cell precursors at the CD69(+)CCR7(+)CCR9(-) stage. Our results demonstrate a differential requirement for the thymic medulla in relation to CD4 conventional and Foxp3(+) thymocyte lineages, in which an intact mTEC compartment is a prerequisite for Foxp3(+) nTreg cell development through the generation of Foxp3(-)CD25(+) nTreg cell precursors.
Original language | English |
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Pages (from-to) | 675-81 |
Number of pages | 7 |
Journal | The Journal of Experimental Medicine |
Volume | 210 |
Issue number | 4 |
DOIs | |
Publication status | Published - 8 Apr 2013 |
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Dive into the research topics of 'The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development'. Together they form a unique fingerprint.Projects
- 3 Finished
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Cortical Thymic Epithelium: Defining Developmental Pathways and Specialisation for Positive Selection
3/01/11 → 2/01/14
Project: Research Councils
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Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G., Jenkinson, E. & Lane, P.
1/10/10 → 30/09/15
Project: Research Councils
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MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)
Jenkinson, E.
3/08/09 → 30/09/17
Project: Research Councils