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

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 ?? T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant V?5(+) 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 V?5(+) ?? T cells during thymus medulla formation for ?? T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation.

SUBMITTER: Roberts NA 

PROVIDER: S-EPMC3368267 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature