A role for CD8 in limiting degeneracy of thymocyte selection

The introduction of a soluble TCR (sTCR) recognizing class I major histocompatibility complex (MHC) in the fetal thymic microenvironment in vitro produces the selection of thymocytes with enhanced avidity for self class I MHC (8). The sTCR was supposed to impose enhanced avidity for self MHC at an early degenerate phase of TCR-driven selection. This could determine increased reactivity to self at later stages of differentiation when specificity of TCR-ligand interaction augments and the effect of sTCR vanishes. This hypothesis was based on the observed deletion of CD4+8+ thymocytes upon upregulation of TCR and the increase in cell size of some CD8+ cells which are expanded in long-term fetal thymus organ cultures (FTOC) as well as in the periphery of adoptively transferred nude mice. Here we show that the developing alphabeta thymocyte which does not express CD8 at the cell surface has a selective advantage in FTOC with sTCR, thus suggesting that participation of CD8 in self peptide/MHC recognition confers specificity to T-cell selection and results in excessive signaling in thymocytes in spite of the presence of sTCR.