Different doses of agonistic ligand drive the maturation of functional CD4and CD8 T cells from immature precursors

MHC molecules are normally required for the development of thymocytes from the CD4(+)CD8(+) double-positive to the CD4 or CD8 single-positive stage. H ere we show that mitogenic plant lectins can substitute for MHC molecules i n driving the differentiation of phenotypically and functionally mature CD4 as well as CD8 T cells. Interestingly, lectin dosage determines whether CD 4 or CD8 cells are generated, indicating that variation of cumulative signa l strength (not necessarily signal quality) can result in an apparent switc hing of lineage preference. Thymocyte perception of differentiation-inducin g signals is modulated by the cellular context, since stimuli that yield CD 8 cells in the context of the thymic microenvironment fail to do so in susp ension culture and generate CD4 progeny instead. Finally, we show that lect in-generated single-positive thymocytes retain the ability to respond to th e ligands initially used to drive their differentiation. Our results call i nto question generalizations and predictions made from other experimental s ystems and reveal that thymocyte selection is considerably more flexible th an had been anticipated.