| First Author | Cowan JE | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 4 | Pages | 675-81 |
| PubMed ID | 23530124 | Mgi Jnum | J:198218 |
| Mgi Id | MGI:5495869 | Doi | 10.1084/jem.20122070 |
| Citation | Cowan JE, et al. (2013) The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J Exp Med 210(4):675-81 |
| abstractText | 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 alphabeta T cell development, including the generation of Foxp3(+) natural regulatory T cells (nTreg cells) and the continued maturation of positively selected conventional alphabeta 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. |
