PRECOMMITMENT OF CD4+CD8+ THYMOCYTES TO EITHER CD4 OR CD8 LINEAGES

CD4+ and CD8+ mature T cells arise from CD4+CD8+ precursors in the thy mus. During this process, cells expressing T-cell receptors (TCRs) rea ctive with self major histocompatibility complex (MHC) class I or II m olecules are positively selected to the CD8 or CD4 lineage, respective ly. It is controversial whether lineage commitment of CD4+CD8+ thymocy tes is controlled directly by TCR specificity for MHC (instructional m odel) or, alternatively, by processes that operate independently of TC R specificity (stochastic model). We show here that CD4+CD8+ thymocyte s bearing a MHC class I-restricted transgenic TCR can be subject to tw o alternative developmental fates. One population of CD4+CD8+ cells is positively selected by MHC class I molecules to the CD8 lineage as ex pected, whereas the other CD4+CD8+ population rearranges endogenous TC R genes and is positively selected by MHC class II molecules to the CD 4 lineage. Blocking TCR-MHC class II interactions in vivo does not int erfere with the generation of CD4+CD8+ cells expressing endogenous TCR s but does prevent their subsequent maturation to CD4+ cells. These da ta support a version of the stochastic model in which CD4+CD8+ thymocy tes are precommitted to the CD4 or CD8 lineage independently of TCR sp ecificity for MHC and prior to positive selection.