PROTEIN MALNUTRITION &HELPER T CELL SUPPORT OF SIGA

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.