Frequency-Analysis of Precursors of Cytotoxic T Lymphocytes in Radiation Chimeras: Enumeration of Antigenspecific CTL-P Restricted to Thymic MHC- and Bone Marrow-MHC-Determinants

The mechanisms controlling the acquisition of T cell restriction specificity and immunocompetence are, despite of numerous investigations, not well understood. From studies of the CTL-immune responsiveness in thymus- and bone marrow-grafted chimeric mice, it became apparent, that it is the thymus which is crucial not only for the maturation or T cells, but also for the specificity repertoire of the T cells (1,2). From these data it was suggested, that during intra-thymic maturation both mutational events and positive selection mechanisms influence the repertoire such that only T cells restricted to thymic epithelial cell MHC determinants mature and will be exported to the peripheral lymphoid organs (3,4). However, the demonstration of non-thymic MHC restricted CTL in both chimeric (5–7) as well as conventional mice (8–10) are incompatible with models proposing strictly thymus-dependent selection mechanisms. Allo-MHC restricted T cells were found not only within spleen cells, but also within thymocytes of both chimeric (9) and non-chimeric mice (10). Accordingly, both self- and allo-MHC restricted thymocytes mature to immunocompetent T cells.