AGE-DEPENDENT REMODELING OF RAT THYMUS - MORPHOLOGICAL AND CYTOFLUOROMETRIC ANALYSIS FROM BIRTH UP TO ONE-YEAR OF AGE

Structural and phenotypic modifications of rat thymocytes from birth u p to one year of age, i.e. during maturation and at the beginning of t he involutive process of the thymus are described. Since the biologica l significance and the mechanisms of thymic involution are still a mat ter of debate, this study aims at clarifying the complexity of the com pensatory events occurring during this relatively neglected period of time. Thymuses from Sprague-Dawley rats were analyzed morphologically and morphometrically by light and electron microscopy, At the same tim e, thymocyte subsets, isolated from the same animals, were characteriz ed by flow cytometry according to physical parameters and phenotypic m arkers. Results indicate that major changes occur during the first mon th from birth and from six months onward. In particular, already durin g the first weeks after birth, thymocytes undergo a slight reduction o f mitoses associated with an increased number of apoptoses, Moreover, during the same period of time, flow cytometry revealed an expansion o f small thymocytes and changes in thymocyte subsets such as increase o f CD4+CD8+ and CD5+alpha beta TCR- and a decrease of CD4-CD8-, CD4-CD8 + cells. The thymus of adult rats was characterized by time-dependent decrease of both mitoses and apoptoses, progressive physical disconnec tion among cells, increase of necrotic areas and fibrosis. Around one year of age tissue changes were associated with a dramatic reduction o f the population of large thymocytes and the rise of numerous small th ymocytes that were unexpectedly negative for all tested markers. By co ntrast, medium-size thymocytes exhibited a marked decrease of CD4+CD8 and CD5+alpha beta TCR- subsets. In conclusion, our data indicate tha t thymus undergoes, with time, a complex remodeling and suggest that t hymic involution is not only a simple shrinkage of the organ but rathe r the result of a series of compensatory mechanisms among different ce ll populations in a setting of progressive involution.