Thymus Epithelial Cell Reaggregate Grafts

Abstract

In the thymus, a unique three-dimensional microenvironment fosters the development of T lymphocytes. T cell progenitors are attracted to the thymus from the circulation by enigmatic molecular and cellular mechanisms. Following colonization, thymocytes undergo a highly ordered developmental process involving several phenotypically and functionally distinct steps. First, signalling via growth factor receptors mediates proliferation and protection from growth factor withdrawal-mediated apoptosis, thus facilitating expansion of the small pool of pro-T cells (“growth factor expansion phase” [reviewed by DiSanto and Rodewald 1998]. Second, β, γ and δ T cell antigen receptor (TCR) genes are rearranged. Thymocytes expressing a productive TCR β chain assembled into the pre-TCR complex are selected for further development, a process accompanied by massive proliferation (“β selection”) [von Boehmer and Fehling 1997]. Third, thymocytes replace the pre-TCR α chain by highly diverse TCR α chains, assemble complete αβ TCRs, and are selected based on the specificity of these receptors to yield self-tolerant (“negative selection”), MHC-restricted (“positive selection”) T cells (collectively termed “αβ selection”) [Kisielow and von Boehmer 1995]. Thymocytes undergo further differentiation as CD4 or CD8 single-positive cells before they can head as antigen-reactive T cells for the peripheral lymphoid organs.