Heterochronic parabiosis: allowing the dissection of the aged immune system (LYM2P.723)

Abstract Parabiosis is the surgical union of two organisms resulting in the development of a single, shared circulatory system. When animals of different ages are conjoined (i.e. heterochronic parabiosis), blood-borne factors from the younger animal can often beneficially affect the older animal and recapitulate the youthful phenotype & function in target tissues. However, the effects of heterochronic parabiosis on the aged immune system remain unexplored. An important question to be answered is whether the cellular defects involved in the aged immune system are due to intrinsic deficiencies or if they can be rescued by extrinsic factors. Also, T cell ontogenesis is known to diminish with age due to thymic involution as well as defects in lymphopoiesis that affect pre-T cells. The heterochronic parabiosis model allows testing of contributions of the aged thymus, pre-T cells and of systemic environment in immune aging. The preliminary data demonstrate differential migration patterns of T cells, B cells & dendritic cells as a function of age. Of interest, pre-T cells from either animal adequately seed the opposing thymus and undergo thymopoiesis and other data suggest that there are no intrinsic defects in old thymocytes, but rather of the old thymic environment. That latter defect may not be corrected by heterochronic parabiosis.