INTERDEPENDENCE OF CORTICAL THYMIC EPITHELIAL-CELL DIFFERENTIATION AND T-LINEAGE COMMITMENT

Thymocyte and thymic epithelial cell (TEC) development are interdepend ent processes. Although lineage relationships among progressively matu ring thymocyte subsets have been characterized, the developmental rela tionships among TEC subsets are obscure. Because epithelial cells expr ess distinct keratin (K) species as a function of differentiation stag e and proliferative status, we used K expression patterns to identify mouse TEC subsets and determine their lineage relationships. As expect ed, cortical and medullary TEC subsets express distinct K expression p atterns in the normal thymus. However, we detected two distinct cortic al TEC subsets, a major K8(+)K5(-) subset and a minor K8(+)K5(+) subse t, which is highly represented at the cortico-medullary junction. Both cortical TEC subsets are also present in recombination activating gen e 1 (RAG-1(-/-)) and TCR beta x delta(-/-) thymi in which T-cell devel opment is blocked at the CD4(-)CD8(-)CD25(+)CD44(-) pre-T cell stage, In contrast, K8(+)K5(+) TECs predominate in the thymi of human CD3 eps ilon transgenic mice in which thymocyte development is blocked at an e arlier CD4(-)CD8(-)CD25(-)CD44(+) stage. Transplantation of newborn hu man CD3 epsilon transgenic thymi under the kidney capsule of RAG-1(-/- ) mice results in the emergence of K8(+)K5(-) TECs concomitant with th e appearance of CD25(+) thymocytes, Together, the data suggest that co rtical TEC development proceeds from a K8(+)K5(+) precursor subset to a K8(+)K5(-) stage in a differentiation process concomitant with T-cel l lineage commitment.