Thymic Involution: Effect on T Cell Differentiation

Abstract

The thymus of long-lived BC3F1 mice involutes progressively throughout life, beginning at 6 weeks of age. This is manifested by the loss of cortical lymphoid mass and by the degenerative changes in epithelial cells. The purpose of this study was to determine to what extent age-related degenerative changes of the thymus affect its capacity to influence the maturation of thymic-derived (T) cells. Accordingly, thymic lobes of mice ranging in age from 1 day to 33 months were implanted under the kidney capsule of T cell-deprived syngeneic young adult TXB mice, and the emergence of T cells was assessed kinetically by various morphologic and functional indices which may be reflective of different T cell subpopulations. They are: a) histology of the thymus graft, b) lymphocyte repopulation of the T cell-dependent areas of lymph nodes, c) total number of splenic lymphocytes carrying θ antigens (θ+), d) T cell-dependent humoral immune response and e) proliferative response of splenic cells to plant lectins, phytohe-magglutinin (PHA) and succinyl-concanavalin A (s-Con A), and allogeneic lymphocytes. The results revealed that the T cell-transforming influence of thymic tissues generally decreases with increasing age. The difference in the patterns of recovery of the various indices of thymus-grafted TXB mice suggests that the extent to which T cells can mature is dependent upon the degree of involution the thymic tissue has undergone with age. In particular, thymic tissues lose the capacity to influence the following functions with advancing age: 1) lymphocyte repopulation of the T cell-dependent areas of lymph nodes; 2) mitogenic reactivity of splenic cells to T cell-specific mitogens (PHA and s-Con A); 3) number of splenic θ+ lymphocytes and splenic T cell helper function; and 4) mitogenic reactivity of splenic T cells to allogeneic lymphocytes.