Early Steps in T Cell Development Are Affected by Aging

Involution of the thymus accompanies aging, a process in which the organ diminishes in size and cellularity and becomes disorganized. The rate of T cell emigration from the thymus is markedly reduced with age, and phenotypic analyses have identified alterations in the relative proportions of the major thymocyte subpopulations. The present studies made use of the capacity of the thymus to regenerate following irradiation from an intrathymic radio-resistant precursor population. By analysis of the differentiation of this “wave” of thymocytes, it was determined that aging most severely affects the earliest developmental transitions. While the overall rate of differentiation does not appear to be affected in older mice, fewer thymic progenitors initiate differentiation. The reduced expansion of late pre-T cells in the middle-aged is due to the smaller pool size of these cells.