We have demonstrated that moderate dietary deficiencies of protein and zinc are accompanied by alterations of cell-mediated and humoral immune responses in Mycobacterium bovis BCG- vaccinated outbred guinea pigs. The ability of BCG vaccine to protect guinea pigs against respiratory challenge with virulent M. tuberculosis is abolished in protein-deficient animals. Our long- range objective is to elucidate the cellular and molecular mechanisms by which malnutrition interferes with BCG vaccine efficacy. This knowledge is critical to the use of BCG vaccine as the only practical means of controlling tuberculosis throughout the world. We have adapted our model of respiratory tuberculosis to inbred guinea pigs (Strain 2) to allow passive transfer and co- culture of lymphoid cells between syngeneic animals. A number of hypotheses will be tested to explain diet-mediated loss of BCG vaccine protection, including helper and suppressor T cell subsets, the number, distribution and lymphokine-producing capability of purified T cells from malnourished guinea pigs, and production of interleukin 1 (IL-1) and interleukin 2 (IL-2) by alveolar macrophages and T cells, respectively. We will utilize specific markers for guinea pig T lymphocytes (rabbit erythrocyte rosette formation; monoclonal pan-T cell antibodies) to enumerate and separate T cells by flow cytometry. Reconstitution of malnourished, immunosuppressed guinea pigs by adoptive transfer purified syngeneic T cells and/or IL-2 will help to pinpoint the specific immunologic lesion(s) induced by protein- and zinc- deficient diets. This information will help to devise approaches to the use of BCG vaccine in malnourished populations which will insure maximum protection against tuberculosis.
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