Immune system plasticity during aging: Immunomodulatory capacity of oestrogens

Advanced age is associated with deleterious changes in both adaptive and innate immunity leading to increased susceptibility to infections and autoimmunity and to diminished responses to vaccination. The effects of aging are most prominent in the T-cell compartment and are causally related to thymic involution. Thus, thymic reconstitution represents a target to moderate/reverse the detrimental impact of aging on the immune system. Although ovariectomy increases thymic T-cell output in young and middle-aged rodents, its effects on the thymus in older animals are rather limited. Moreover, reports concerning the direct effects of oestrogens on T cells in the periphery and dendritic cells (DCs) and macrophages (M?s) that could, in turn affect T-cell performance in older age are conflicting. Therefore, this project is designed to reach two goals. First, to identify the critical age-related changes at the T-cell level that underlay the decline in rat T-cell-dependent immune responses (by analysing the response to influenza vaccine) and alterations in T-cell tolerance (by examining development of experimental autoimmune encephalomyelitis and collagen-induced arthritis), in addition to mapping the corresponding thymic defects and DC and M? malfunctions. Second, to explore oestrogen action on immune cells, as well as the possibility of enhancing the immune functional capacity in aging females via pharmacological manipulation with oestrogens without increasing risk of autoimmunity.