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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.

Original publication

DOI

10.1016/j.immuni.2012.01.016

Type

Journal article

Journal

Immunity

Publication Date

23/03/2012

Volume

36

Pages

427 - 437

Keywords

Animals, Cell Differentiation, Cellular Microenvironment, Epithelial Cells, Female, Fetus, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Precursor Cells, T-Lymphoid, Pregnancy, Receptor Activator of Nuclear Factor-kappa B, Receptors, Antigen, T-Cell, gamma-delta, Signal Transduction, Thymus Gland, Transcription Factors