Specialisation of thymic epithelial cells for positive selection of CD4+8+ thymocytes

Following their migration into the thymus, hemopoeitic stem cell precursors enter a complex developmental pathway involving proliferation, differentiation and alpha betaT-cell receptor (alpha beta TCR)-mediated selection procedures, in order to generate mature T-cell populations ready for export to the periphery. Thus, a critical stage during intrathymic T-cell development involves the generation of functionally mature CD4(+)8(-) and CD4(-)8(+) cells from immature CD4(+)8(+) precursor thymocytes, a poorly understood process referred to as positive selection. While interactions between the alpha beta TCR and MHC-peptide complexes are known to be essential for the initiation of positive selection, additional unknown signals are also required. Using an in vitro reaggregate thymic organ culture system which allows comparison of the abilities of various cell types to induce maturation of CD4(+)8(+) precursors, we provide evidence that both MHC-peptide complexes and specialised accessory molecules must be provided by thymic epithelium for efficient mediation of positive selection. Moreover, analysis of positive selection in the presence of thymic and non-thymic stromal cells expressing MHC class II molecules with the same limited peptide array suggests that this unique ability of thymic epithelium to mediate positive selection of CD4(+)8(-) cells is not solely due to presentation of a specialised peptide repertoire, but is dependent upon provision of specialised accessory interactions.