Vitamin A Status and the Immune Response to Pneumococcal Polysaccharide: Effects of Age and Early Stages of Retinol Deficiency in Rats

Abstract

Production of antibodies to pneumococcal polysaccharide from Streptococcus pneumoniae, type III was determined in young rats at different ages and stages of vitamin A deficiency. At 30, 35 and 45 d of age, serum retinol concentrations of vitamin A-depleted rats were 46, 35 and 9%, respectively, of the serum retinol concentrations of pair-fed controls. Specific antibody production was low at 30 d of age for both vitamin A-depleted rats and control rats. Between 30 and 45 d of age, antibody production increased considerably in normal rats; however, the response of vitamin A-depleted rats was only 22% (P less than or equal to 0.001) that of controls at 35 d of age and 8% that of controls (P less than or equal to 0.001) for 45-d-old rats. Lymphocyte populations were examined by flow cytometry. The numbers of immunoglobulin M- and immunoglobulin D-positive cells changed with age, but not as a result of dietary treatment. The numbers of total T cells or helper and suppressor T cell subsets did not differ with age or with vitamin A status. These studies showed that the normal antibody response to pneumococcal polysaccharide develops rapidly after 30 d of age in the rat, that this antibody response is impaired even during the early stages of vitamin A deficiency, and that impaired antibody production does not seem to be accompanied by quantitative differences in splenic lymphocyte populations.

Vitamin A Status: Relationship to Immunity and the Antibody Response

“…Surprisingly, vitamin A deficiency did not result in significant shifts in the percentage of total T cells or the distribution ofT cell subsets (helper and suppressor/ cytotoxic) or of IgM-or IgD-positive B lymphocytes (18,36). This picture contrasts with that reported for human protein-energy malnutrition, in which the fraction of helper (CD4+) T cells was reported to be decreased (37).…”

“…In all experiments, repletion with vitamin A (equal to 1.5 mg of retinol given orally) completely restored a normal level of antibody production, even in rats with symptoms of vitamin A deficiency, showing that this impairment is reversible and causally related to a dificiency of vitamin A. In studies that examined the ontogeny of antibody production, a significant reduction in the IgM response specific for pneumococcal polysaccharide was detectable as early as 35 days of age (36).…”

“…In animal studies, chronic high-dose supplementation decreased resistance to infection, suppressed the antibody response, and decreased lymphocyte proliferation (49), but an acute large dose of vitamin A restored the immune response in the previously vitamin A-deficient rat or chick (31,49,77). When vitamin A-deficient rats were given single large doses of retinol at the time of immunization with pneumococcal polysaccharide, the antibody response was restored to near-normal levels and no outward signs of toxicity were observed (36). The response to tetanus toxoid of rats given a single moderate dose of retinol 1 day after immunization with tetanus toxoid was slightly greater than the normal response (59).…”

“…Analysis of the major T and B cell populations of the spleens of vitamin A-deficient and normal rats has been performed using fluorescent antibodies specific for total T cells, T cell subsets, or B lymphocytes (18,36). Surprisingly, vitamin A deficiency did not result in significant shifts in the percentage of total T cells or the distribution ofT cell subsets (helper and suppressor/ cytotoxic) or of IgM-or IgD-positive B lymphocytes (18,36).…”

Vitamin A potentiates CpG-mediated memory B-cell proliferation and differentiation: involvement of early activation of p38MAPK

“…Some reports document that retinoids are required for B-cell activity 12 and have the potential to enhance differentiation and antibody responses of B cells, [13][14][15][16] and that B-cell responses are impaired in vitamin A-deficient rats. 17 We have previously shown that RA inhibits the proliferation of human and murine B-cell precursors 18 as well as peripheral-blood B cells stimulated via B-cell receptor (BcR). 19 We also demonstrated that the inhibition of B-cell proliferation was accompanied by inhibition of the cell-cycle machinery driving the cells from G 1 to S phase.…”