The importance of nutritional factors in the ability to mount an immune response to bacterial infection is not yet well understood. This proposal focuses on the role of vitamin A nutritional status early in life on the immune response to bacterial antigens, particularly to the capsular polysaccharide antigen of Streptococcus pneumoniae, Type III (designated SSS-III). Using the young rat as our experimental model, we have conducted preliminary studies which indicate that young rats fed a retinol-deficient diet have impaired antibody production when immunized with SSS-III, even before any clinical signs of vitamin A deficiency are observed. We will conduct studies under five Specific Aims to test a number of hypotheses.
In Aim 1, we will test the hypothesis that, although nutritional retinol depletion compromises the young rat's antibody production to SSS-III, rehabilitation with retinol very near the time of immunization will restore normal antibody production. We will first determine the minimal length of time prior to immunization that retinol must be provided in order to restore immune function, and we will then determine the optimal amount of retinol needed to effectively restore antibody production. In a limited manner, we will compare the effects of vitamin A depletion and repletion on two other antigens of clinical importance, the lipopolysaccharide from Pseudomonas aeruginosa and meningococcal Type C antigen from Nesseria meningitidis.
In Aim 2, we will develop methods for immunization of spleen cells with SSS-III, in vitro, in order to investigate which specific cell types are affected by impaired retinol status.
In Aim 3, we will conduct, in vivo, cell transfer studies in which populations of T cells shown to either amplify or suppress the antibody response to SSS-III will be transferred either to or from retinol-depleted animals, after which antibody production in vivo will be assessed. Together, Aims 2 and 3 should provide a much more detailed understanding of the cell types that regulate the immune response to SSS-III.
In Aim 4, we will determine the effect of dietary retinol status on the production of interleukin-2 and gamma-interferon, two molecules that are of particular importance in modulating the humoral immune response. Finally, the goal of Aim 5 is to quantitate tissue retinoids in these animals in order to correlate the concentration of retinol in lymphoid organs, plasma and liver with the animal's immune response. These studies are expected to provide new information on the role of retinol status in vivo on antibody production to clinically relevant bacterial antigens.
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