Seeding of thymic microenvironments defined by distinct thymocyte-stromal cell interactions is developmentally controlled.

Seeding of distinct intrathymic microenvironments defined by direct thymocyte-stromal cell interactions was correlated with T cell development in situ using radiation and nonradiation chimeras of Thy-1.1/1.2 congenic mice. The results identify associations of thymocytes with I-A- macrophages in the cortex as the earliest discernible cell-cell interactions during thymopoiesis. After a significant delay, this recognition stage is followed by concomitant interactions of T cells with I-A+ epithelial cells in the cortex and bone marrow-derived I-A+ dendritic cells in the medulla. All three types of T cell-stromal cell interactions occur after seeding of the intrathymic precursor cell subset and before development of mature medullary-type T cells. The seeding kinetics imply that recognition of cortical epithelial cells by thymocytes in situ represents a relatively late stage of cortical T cell development, whereas thymocyte-dendritic cell interactions denote a very early stage of T cell development in the medulla. The relative positioning of these cell-cell recognition stages during the course of T cell maturation pertains to a putative role of these microenvironments in selection and tolerization of the T cell repertoire.