The disordered state of immunologic regulation that contributes to the development of autoimmunity, renal disease and shortened life span in several auto-immune prone mice can be modulated by restricting food and calorie intake. This proposal further dissects the nutritional and immunologic mechanisms involved in the inhibition of autoimmune disease in (NZB X NZW)F1, C57BL/1pr and BXSB mice. Each of these murine strains has a unique immunologic and genetic defect predisposing to disease. Our current hypothesis is that food restriction ameliorates autoimmune disease by influencing cellular immune function. Cell changes may involve cell cycle, change in subsets of lymphocytes and macrophages, change in cell surface density of antigens and changes in the production and utilization of lymphokines. We will focus our studies on these key aspects of cellular immunity, studying both restricted food intake and the protective influence of essential fatty acid deficiency in these autoimmune-prone mice. We will examine age-associated functional changes in both post-thymic and pre-thymic T cell populations which could result from alterations in the stromal and hormonal inductive capacity caused by restricted food intake. We will use the FACS IV cell sorter to analyze the cell surface antigen density and to enumerate the proportion of lymphocyte numbers in different lymphoid tissues of mice fed various diets throughout their life span. Further, because dietary fat intake can modulate prostaglandin (PG) production and response in lymphoid tissues, we plan to measure PG levels that may inhibit immune function. In addition, we will study if food restriction imposed at an adult-age facilitates further the therapeutic effects of sex hormone (androgen) in-vivo to prevent the progression and severity of autoimmune disease. The scientific disciplines followed include immunology, nutrition and pathology. The proposed studies undertaken in inbred strains of mice will contribute to a better understanding of the relationship of nutritional factors on the development of autoimmunity in mice and eventually in man.
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