PROTEIN MALNUTRITION & HELPER T CELL SUPPORT OF SIGA

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The major objective of the proposed research is to determine the etiology of the impaired secretory immunoglobulin (sIg) A production observed during dietary protein deficiency. This impairment likely contributes to the enhanced microbial infection or colonization of oral and mucosal surfaces during protein malnutrition. Total and antigen-specific secretory (S) IgA (following oral challenge with Giardia muris or Streptococcus mutans in saliva and intestinal secretions, using enzyme immunoassay (ETA), will be determine in mice fed 20% (20C) or 4% (4C) casein diets form weaning. The significance of sIgA reduction will be demonstrated by evaluating the ability of oral or intestinal pathogens to colonize at the respective surfaces. The hypthesis that dietary protein reductions reduces IgA by altering specific T cell subsets associated with help (H) (L3T4+) or suppression (S) (Lyt 2+), of the IgA immune response will be tested. Histological identification and quantification of T cell subsets in excised salivary glands, Peyer's patches, and spleen of mice fed 4C or 20C before and after infection will entail immunofluorescence using antibodies to L3T4 or Lyt2. Using the same antibodies, each subset will be isolated from dispersed tissues by "panning"; and the ability to generate IgA-enhancing factors will be evaluated before and during infection. L3T4+ T cell IgA enhancing lymphokines included, Interleukin 5 (IL5), IL4, IL2. Polyclonally stimulated T cell supernatants will be tested using EIA for the ability to promote IgA production, as opposed to IgG, IgG1 and IgM, production from purified B cells stimulated with lipopolysaccharide (LPS). Since IL4, IL5 could be generated by HT cell subsets distinct from IL2-generating HT cell subsets, the frequency of each subset in these tissues will be estimated using limiting dilution analysis. Noting the IgA-enhancing lymphokine which is impaired in mice fed 4C, attempts will be made to reconstitute the secretory IgA levels in mice fed 4C by treatment with the appropiate recombinant lymphokine. This research will contribute to understanding the problems of oral health in malnourished human populations as they relate to decreased secretory immunity and oral health.