We have examined the intra-thymic differentiation of functionally and phenotypically distinct T cell subsets as well as their interaction with thymic epithelium. Studies on thymocytes from genetically defective scid mice have suggested that TcR+ cells play a critical role in promoting the entry of thymocytes into the CD4/CD8 differentiation pathway as well as in promoting the maturation and organization of thymic medullary epithelium. Phenotypic studies on developing thymocytes have identified two distinct, but inter-related subsets of thymocytes that express identically skewed TCR repertoires, namely CD4-CD8-TCRalpha-beta+ thymocytes and Ly6C+ thymocytes. Ly6C+ thymocytes were found to represent a readily identifiably subpopulation within each CD4/CD8 thymocyte subset; nevertheless, the Ly6C+ thymocytes within each CD4/CD8 thymocyte subset expressed a distinctive TCR repertoire marked by overexpression of V-beta-8 and expression of autoreactive TCR. Finally, we found that thymocytes readily acquire surface CD4 and CD8 determinants from other thymocytes, demonstrating that caution is necessary in using low level CD4/CD8 expression to identify novel thymocyte subsets.
