The thymus has a central role in directing the maturation and differentiation of T cells1. These processes involve movement of cells of haematopoietic origin through the thymus and are supposed to require ultimate physical contact between T lymphocytes and cells of the thymic epithelium. Cytotoxic T cells (CTLs) induced by virus-infected or hapten-modified autologous cells exhibit dual specificity: for the products of the self major histocompatibility complex (MHC, H-2 in the mouse) and for the foreign antigen2-5. It has been proposed that 'self' specificity of MHC-restricted CTLs is determined by the MHC-encoded antigens expressed on the surface of thymic epithelial cells6. We show here that the differentiation of MHC-restricted CTLs can take place without thymic influence. In these experiments, self-MHC-restricted CTLs differentiate from spleen cells of nu/nu mice which lack thymuses after stimulation with 2,4,6-trinitrophenyl (TNP)-coupled autologous cells in the presence of T-cell growth factor.
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