Thoughts on the thymus and the T-lymphocyte repertoire. Relevance to the tolerance of the immune response

The thymus is a central lymphoid organ, and has one important function in the immune system. It generates immunocompetent T (= thymus-dependent) cells. 'Immunocompetence' is the single most important characteristic acquired during the differentiation process of T-cells, from progenitor cell in the bone marrow to mature cell in peripheral lymphoid organs and blood. The basis of competence is recognition, mediated by the T-cell receptor on the cell surface. Using this receptor, T-cells recognize antigens only in the form of antigenic fragments complexed with molecules of the major histocompatibility complex. Within the thymus, progenitor cells rearrange gene segments encoding the various parts of the receptor molecule. After expression of all possible receptors (the potentially available repertoire) selection processes occur, yielding only those T-cells that have a receptor by which antigens can be recognized together with molecules of the major histocompatibility complex, and that do not recognize autoantigens (the actual repertoire). This process of selection is considered as a unique function of the thymus. In this review, first some histophysiological aspects of the thymus are described. Next, the events that occur during the sojourn of the lymphocytes in the thymus are presented. Finally, these data are considered with regard to thymic abnormalities. These include acute and age-associated involution, and the generation of autoimmune reactivity due to disturbed intrathymic selection.