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Immunity. 2012 Mar 23;36(3):427-37. doi: 10.1016/j.immuni.2012.01.016. Epub 2012 Mar 15.

Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium.

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1
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, B15 2TT, UK.

Abstract

The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant Vγ5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5(+) γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation.

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PMID:
22425250
PMCID:
PMC3368267
DOI:
10.1016/j.immuni.2012.01.016
[Indexed for MEDLINE]
Free PMC Article

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