Individual T cell populations are characterized by specific surface proteins, 
namely by the T cell receptor complex (TCR) and by two accessory molecules, CD8 
(Lyt2) and CD4 (L3T4). CD8 and CD4 are required for T cell interactions with 
class I or class II major histocompatibility complex molecules. In the thymus, 
immature CD8(-4)-TCR- cells differentiate, possibly via a short stage of CD8+4- 
thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell 
populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T 
helper cells. In order to analyse the differentiation steps involving CD8, we 
generated transgenic mice expressing mu heavy chain genes from an anti-Lyt2.2 
hybridoma. Transgenic lines expressing either the complete (mu sm) or only the 
secreted mu protein (mu s) suffer from a severe depletion of their CD8+4+ 
thymocytes affecting also the mature CD8+4- and CD4+8- populations. The 
depletion is correlated to the expression of transgenic mu-chain proteins within 
thymocytes. This intrathymocyte expression of the mu chain prevents CD8-4- 
thymocytes from further differentiation, most probably via intracellular 
interactions between mu heavy chain and CD8 proteins. These results show that 
CD8 plays an important role during thymocyte maturation.