Revisiting the Road Map of Medullary Thymic Epithelial Cell Differentiation

The basic two-step terminal differentiation model of the medullary thymic epithelial cell (mTEC) lineage from immature MHC class II (MHCII) lo to mature MHCII hi mTECs has recently been extended to include a third stage, namely the post-Aire MHCII lo subset as identified by lineage-tracing models. However, a suitable surface marker distinguishing the phenotypically overlapping pre- from the post-Aire MHCII lo stage has been lacking. In this study, we introduce the lectin Tetragonolobus purpureas agglutinin (TPA) as a novel cell surface marker that allows for such delineation. Based on our data, we derived the following sequence of mTEC differentiation: TPA lo MHCII lo → TPA lo MHCII hi → TPA hi MHCII hi → TPA hi MHCII lo . Surprisingly, in the steady-state postnatal thymus TPA lo MHCII lo pre-Aire rather than terminally differentiated post-Aire TPA hi MHCII lo mTECs were marked for apoptosis at an exceptionally high rate of ∼70%. Hence, only the minor cycling fraction of the MHCII lo subset ( lo mTECs points to a “quality control” step during early mTEC differentiation.