Although there is good evidence of decreased T cell functions with advancing age in mice and men, the mechanism for such a decline is still undefined. The goal of the proposed studies is to clarify the possible mechanisms of the age-related decline of T cell function in mice. This will be done by analyzing the contribution of precursor cells (hemopoietic stem cells, restricted progenitors, etc.), the thymus proper and host factors in determining the intrathymic and extrathymic steps involved in T cell differentiation. By """"""""heterochronic"""""""" transplantation of these different components into hosts of different ages, and the use of chromosome markers, surface antigens and other functional properties (which have enabled us in the past to define the role of thymus traffic and of postthymic maturation in mice) we will try to define the mechanisms of the age-related decline of T cell function. """"""""Heterochronic"""""""" transplantation means the use of """"""""young"""""""" and """"""""old"""""""" hemopoietic cells, thymus and recipient hosts in the different logical permutations which will permit an assessment of the functional capacity of each component. Postthymic maturation will also be studied, using heterochronic transplantation of postthymic precursor (PTP) cells in association with thymus in cell-impermeable diffusion chambers and T cell-deficient hosts. Again, the three components (PTP cells, thymus and hosts) will be derived from young and old mice, in attempts to determine the role of aging in each component. The understanding of the age-related decline of T cell function will, obviously, increase our knowledge of the basic mechanisms of T cell development, as well as increase our knowledge of the mechanisms of immunological aging.
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