Thymocytes positively select thymocytes in human system.

We previously demonstrated the expression of MHC class II molecules in a significant percentage of human fetal and postnatal thymocytes. These results, at that time, raised the question as to whether the MHC class II molecules on immature thymocytes could actively be involved in the selection of immature T cells. We have developed a human reaggregate culture system to address this issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have been shown to be a major selecting cell type of positive selection, we were clearly able to see the involvement of MHC class II+ thymocytes during selection process through T-T interaction. In addition, maturation to single positive (SP) cells occurred only in the presence of MHC class II molecules and immature thymocytes were found to be arrested at the double positive (DP) stage of differentiation by blocking of TCR recognition of MHC class II molecules. All these results strongly suggest that human MHC class II+ thymocytes actively participate in the selection of the TCR repertoire, for which TCR recognition of peptide/MHC class II may be an initial determining step.