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.
journal_name
Immunityjournal_title
Immunityauthors
Roberts NA,White AJ,Jenkinson WE,Turchinovich G,Nakamura K,Withers DR,McConnell FM,Desanti GE,Benezech C,Parnell SM,Cunningham AF,Paolino M,Penninger JM,Simon AK,Nitta T,Ohigashi I,Takahama Y,Caamano JH,Hayday AC,Ladoi
10.1016/j.immuni.2012.01.016subject
Has Abstractpub_date
2012-03-23 00:00:00pages
427-37issue
3eissn
1074-7613issn
1097-4180pii
S1074-7613(12)00089-1journal_volume
36pub_type
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