Immunity
Volume 36, Issue 3, 23 March 2012, Pages 427-437
Journal home page for Immunity

Article
Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium

https://doi.org/10.1016/j.immuni.2012.01.016Get rights and content
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Summary

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.

Highlights

► Invariant Vγ5+ thymocytes regulate formation of Aire+ medullary thymic epithelium ► Generation of an invariant Vγ5+ T cell population requires thymus medulla development ► Skint-1-mediated Vγ5+ thymocyte development is Aire independent ► Dependency on Tnfrsf11a links γδ T cell and medullary epithelium development

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Present address: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA

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These authors contributed equally to this work