Intrathymic T-cell development is dependent upon signals provided by the thymic stromal cell microenvironment. However, loss o [tbymic T cells in natural and experimentally induced situations is associated with a reduction in the surrounding epithelium, suggesting an interdependence between tbymocytes and their microenvironment. Here, the authors review the evidence in [avour of this intratbymic symbiosis, and hypothesize that T cells may provide maturation and survival signals that are necessary [or the development and maintenance of their microenvironment.

The thymus has long been known as a source of lymphocytes*'2, although recognition of its role in the production of a specialized population of immune cells (T cells), is more recent:. These findings led to a highly productive phase of research which focused on the developmental steps taken by T cells as they make their way through the thymus, and on the role of the nonlymphoid cells that comprise the thymic'microenvironment'S-* L These stromai cells (epithelial cells, dendritic cells, macrophages, fibroblasts, neurones, etc.) provide different microenvironmental stimuli in different regions of the thymus via direct cell-cell interactions and soluble molecules 7-'s. The intrathymic life of a developing T cell can be viewed as a series of educational experiences, each provided by a distinct region of the microenvironment (Fig. 1) N. Thus, as the developing cells journey through the thymus from the outermost subcapsular region through the cortex and into the central medulla they are provided with signals for proliferation, receptor gene rearrangement, positive selection for major histocompatibility complex (MHC) restriction, negative selection for deletion of self-reactive and defective cells, molecular and functional maturation. Such maturation can be visualized by the phenotype of the developing ceils. Figure 1 shows a simplified view of this process whereby T cells mature from a CD3-4-8-triple negative (subcapsule), through immature CD3" 8" single positive (or, in some mice, CD3-4+) and CD3-PCD4+ 8• double positive (cortex), to mature CD3+ CD4+ and CD3* CD8" single positive (medulla) phenotype. The journey is a difficult and dangeroas one-only 5% of