The thymic compartment responsible for positive selection of CD4⁺ T cells

Our aim was to assess the generality of the observation that positive selection of CD4⁺ T cells is mediated by MHC class II molecules on epithelial cells of the thymic cortex. By appropriate matings of previously established transgenic and mutant mouse lines, we were able to produce animals that lacked MHC class II molecules; individuals expressing only the class II E complex, but in all the usual thymic compartments; animals that had E molecules in the thymic medulla but not in the cortex; and, reciprocally, individuals expressing the E complex in the thymic cortex but essentially not in the medulla. Those mice which displayed class II molecules in the cortex had normal numbers of CD4⁺CD8^- T cells in the thymus and CD4⁺ T cells in the periphery, while 'bare' cortex mice were almost devoid of mature CD4 single positive cells. This finding serves to generalize observations from previous studies of similar design but limited to assaying positive selection of T cells which expressed a single transgenic E-restricted TCR or a subset of V_β6⁺ TCRs.