ovalbumin and Vitamin-A-Deficiency

Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this stage of life. Ovalbumin (OVA) was administered orally to mice through breast milk and efficiency of systemic tolerance to OVA was assessed in adulthood using a model of allergic airway inflammation. Oral tolerance induction was fully efficient starting third week of life. Inefficiency in neonates was a consequence of abnormal antigen transfer across the gut barrier and retinaldehyde dehydrogenase expression by mesenteric lymph node CD103(+) neonatal dendritic cells, resulting in inefficient T-cell activation. Neonates' serum retinol levels were three times lower than in adult mice, and vitamin A supplementation was sufficient to rescue neonatal defects and allow tolerance induction from birth. The establishment of oral tolerance required the differentiation of Th1 lymphocytes in both vitamin A-supplemented neonates and 3-week-old unsupplemented mice. This knowledge should guide the design of interventions for allergy prevention that are adapted to the neonatal stage of life such as vitamin A supplementation.

Topics: Administration, Oral; Animals; Animals, Newborn; Animals, Suckling; Antigens, CD; Dendritic Cells; Gene Expression; Immune Tolerance; Integrin alpha Chains; Lymph Nodes; Lymphocyte Activation; Mesentery; Mice; Mice, Inbred BALB C; Ovalbumin; T-Lymphocytes, Regulatory; Th1 Cells; Vitamin A; Vitamin A Deficiency

Vitamin A (VA) deficiency is one of the most common malnutrition conditions. Recent reports showed that VA plays an important role in the immune balance; lack of VA could result in enhanced type 2 immune response characterized by increased type 2 cytokine production and type 2 innate lymphoid cell infiltration and activation. Type 2 immune response plays protective role in anti-infection but plays pathological role in asthmatic disease. In order to investigate the role of VA in the asthmatic disease, we used ovalbumin-induced asthma murine model and observed the pathological changes between mouse-received VA-deficient and VA-sufficient diets. We also measured the type 2 cytokine expressions to reveal the potential mechanism. Our results showed that VA deficiency exacerbates ovalbumin-induced lung inflammation and type 2 cytokine productions. Thus, VA deficiency, or malnutrition in further extent, may contribute to the increasing prevalence of asthma.

Topics: Animals; Asthma; Cytokines; Inflammation; Mice; Ovalbumin; Transcriptional Activation; Vitamin A Deficiency

Oral tolerance is a phenomenon of induction of systemic unresponsiveness to antigens ingested by the oral route and loss of immune response. Studies have shown the importance of vitamin A in oral tolerance in vitro but not in an in vivo experimental model. Therefore, we carried out experiments to determine how vitamin A deficiency affects tolerance induction and the ability of mesenteric lymph node (MLN) CD11c(+) cells to induce regulatory T cells (Tregs). Immunological tolerance was induced by oral ovalbumin (OVA) administration in vitamin A-sufficient mice. OVA-specific antibody and cytokine production were significantly reduced. On the other hand, in vitamin A-deficient mice, both OVA-specific antibody and cytokine production were not suppressed by oral OVA administration. Regarding induction of Tregs, the conversion rate of Foxp3(+) cells from naïve CD4(+) cell by CD11c(+) cells was decreased in vitamin A-deficient mice. Our study indicates that vitamin A deficiency causes the breakdown of oral tolerance in vivo.

Topics: Administration, Oral; Animals; Antibodies; CD11 Antigens; CD4 Antigens; Cytokines; Forkhead Transcription Factors; Immune Tolerance; Immunity, Active; Lymph Nodes; Mice, Inbred BALB C; Ovalbumin; T-Lymphocytes, Regulatory; Vitamin A; Vitamin A Deficiency

The Th1/Th2 paradigm has become an important issue in the pathogenesis of asthma, characterized by normal Th1 and elevated Th2 cytokine expression. Vitamin A deficiency (VAD) can produce a Th1 bias, whereas high-level dietary vitamin A can promote a Th2 bias. We used the OVA exposure mouse model to determine the contributions of vitamin A-deficient, control (4IU/g), and high-level vitamin A (250-IU/g) diets to the development of allergic airway inflammation and hyperresponsiveness. VAD reduced serum IgE and IgG1 responses, pulmonary eosinophilia, and the levels of IL-4 and IL-5 in bronchoalveolar lavage specimens, whereas the 250-IU/g diet increased serum IgE. Also, VAD blocked pulmonary hyperresponsiveness following methacholine challenge while the 250-IU/g diet exacerbated pulmonary hyperresponsiveness. In conclusion, VAD diminished and high-level dietary vitamin A enhanced the development of experimental asthma in this model system. These data suggest that excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries.

Topics: Animals; Asthma; Body Weight; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Diet; Disease Models, Animal; Female; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-5; Liver; Lung; Macrophages; Male; Mice; Ovalbumin; Pulmonary Eosinophilia; Respiratory Hypersensitivity; Vitamin A; Vitamin A Deficiency

Sixty-eight Angus-based steers (224 +/- 7.6 kg of BW) were used to evaluate the effects of a prolonged dietary vitamin A restriction on marbling and immunocompetency. Steers were allotted randomly to 1 of 2 treatments: LOW (no supplemental vitamin A) and HIGH (diet supplemented with 2,200 IU of vitamin A/kg of DM). Diets contained 60% high-moisture corn, 20% roasted soybeans, 10% corn silage, and 10% of a protein supplement. Steers were penned and fed individually. For the first 141 d, steers were program-fed to achieve a gain of 1.1 kg/d. The last 75 d of the experiment, steers were offered feed for ad libitum intake. At slaughter, serum and liver samples were taken to determine their retinol content. To evaluate immunocompetency, 10 steers per treatment were selected randomly on d 141 and received an ovalbumen vaccine, and 21 d later, the steers were revaccinated. On d 182, blood samples were taken from the vaccinated steers to determine serum antibody titers by ELISA. Steers were slaughtered after 216 d on feed. Carcass characteristics were determined, and LM samples were taken for composition analysis. Subcutaneous fat samples were taken for fatty acid composition analysis. Performance (ADG, DMI, and G:F) was not affected by vitamin A restriction (all P > 0.10). Hot carcass weight, 12th-rib fat, and yield grade did not differ between LOW and HIGH steers (all P > 0.10). Marbling score (LOW = 574 vs. HIGH = 568, P = 0.79) and i.m. fat (LOW = 5.0 vs. HIGH = 4.7% ether-extractable fat, P = 0.57) were not increased by vitamin A restriction. Serum (LOW = 18.7 vs. HIGH = 35.7 mug/dL, P < 0.01) and liver (LOW = 6.3 vs. HIGH = 38.1 mug/g, P < 0.01) retinol levels were lower in LOW steers compared with HIGH steers at slaughter. Response to ovalbumin vaccination was not affected by vitamin A restriction (LOW = 13.1 vs. HIGH = 12.8 log(2) titers, P = 0.60). Slight changes in the fatty acid profile of s.c. fat of the steers were detected. A greater proportion of MUFA (LOW = 41.7 vs. HIGH = 39.9%, P = 0.03) and fewer SFA (LOW = 47.1 vs. 48.7, P = 0.03) were observed in vitamin A-restricted steers. This suggests that vitamin A restriction may affect the activity of desaturase enzyme (desaturase activity index, LOW = 46.9 vs. HIGH = 44.9, P = 0.01). Feeding a low vitamin A diet for 216 d to Angus-based steers did not affect performance, marbling score, or animal health and immunocompetency. Slight changes in the fatty acid profile of s.c. fat were observed, suggestin

Topics: Adipose Tissue; Animal Nutritional Physiological Phenomena; Animals; Antibodies; Body Composition; Cattle; Fatty Acids, Nonesterified; Liver; Male; Meat; Muscle, Skeletal; Ovalbumin; Random Allocation; Vitamin A; Vitamin A Deficiency

Vitamin A deficiency impairs both T helper type 1 (Th1)- and type 2 (Th2)-mediated immune responses, although Th2 responses seem to be principally affected. Multiple mechanisms are involved in this immune suppression, but the hypothesis that deficiency affects development of Th1/Th2 memory cell phenotype has not been tested directly in vivo. To do so, lymphocytes from DO11.10 T cell receptor (TCR)-transgenic mice were transferred to vitamin A-deficient or control BALB/c recipients. Recipients were then immunized with the cognate peptide antigen for the TCR-transgenic DO11.10 T cells (OVA(323-339)). After 2-5 wk, the transferred OVA(323-339)-specific T cells were identified from draining lymph nodes with the TCR-clonotypic antibody KJ1-26, and their Th1/Th2 phenotype was characterized by intracellular cytokine staining after in vitro stimulation with phorbol myristate acetate and ionomycin. The percentage of CD4(+)KJ1-26(+) cells positive for IL-10 was 100% greater in vitamin A-deficient mice (3.49 +/- 0.41%; mean +/- SE) than in control mice (1.74 +/- 0.37%). IL-4 did not differ between groups. In addition, the percentages of CD4(+)KJ1-26(+) cells from vitamin A-deficient mice that were positive for interferon (IFN)-gamma (8.8 +/- 0.73%) and interleukin (IL)-2 (39.5 +/- 3.1%) were both lower than the percentages in control mice (11.4 +/- 0.67 and 47.0 +/- 2.8%, respectively). Thus vitamin A deficiency, at the time of initial antigen exposure, enhances the development of IL-10-producing Th2 or T regulatory cells and diminishes the development of Th1 memory cells.

Topics: Animals; Animals, Newborn; Female; Immunologic Memory; Interleukin-10; Lymph Nodes; Maternal-Fetal Exchange; Mice; Ovalbumin; Peptide Fragments; Pregnancy; Succinimides; Th1 Cells; Th2 Cells; Vitamin A; Vitamin A Deficiency

Retinoids modulate many physiological processes such as the differentiation and growth of different cell types, including cells from the immune system. We have previously shown that retinoids modulate IgE production in vitro and in vivo. In the present study we investigated the effects of retinoids in non-sensitized and ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented with 0.5% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4) responses in non-sensitized mice. After ovalbumin sensitization in the VA-deficient and the ATRA supplementation diet groups, no significant effects on IL-4 production were observed. By contrast, gamma interferon (IFN-gamma production from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base and the ATRA-supplemented diet group. The data indicate that VA and retinoid content in a diet influences the cytokine response in non-sensitized and also ovalbumin-sensitized mice. Therefore these molecules may serve as active modulators of cytokine production in vivo that are responsible for the induction and persistence of atopic diseases.

Topics: Animals; Cells, Cultured; Cytokines; Diet; Female; Flow Cytometry; Immunization; Interferon-gamma; Interleukin-4; Ionomycin; Lymphocyte Count; Lymphocyte Subsets; Lymphocytes; Mice; Ovalbumin; Retinoids; Spleen; Tetradecanoylphorbol Acetate; Tretinoin; Vitamin A Deficiency

Serum cortisol and antigen-specific and polyclonal immunoglobulin G (IgG) concentrations were measured to investigate the relationship between vitamin A status and immune function in lambs. Twenty-four 3-mo-old crossbred ewe lambs weighing approximately 10 kg were each fed 900 g/d of a carotene-deficient diet. The 12 control lambs also received a 100,000 IU oral dose of vitamin A palmitate every 2 wk. All lambs were given primary and secondary antigenic challenges. Lambs were slaughtered at the end of the secondary challenge period. Liver vitamin A concentrations were greater (P less than .001) in the control animals (69.5 vs 1.3 micrograms/g wet tissue). Both groups of lambs exhibited a similar growth response until d 105, after which daily gain of the control lambs exceeded (P less than .03) that of the A-deficient lambs. Polyclonal serum IgG concentrations were greater (P less than .05) in the A-deficient lambs on d 49 to 124 and on d 151 (P less than .10). Ovalbumin-specific serum IgG concentrations tended to be greater in the control lambs throughout the primary and secondary challenge periods. Control lambs had greater titers on d 164 (P less than .07) and d 190 (P less than .03). Vitamin A status appeared to have no consistent effects on serum cortisol concentrations. Spleen weights were greater (P less than .002) in the A-deficient lambs. Lungs from 11 of 12 A-deficient lambs contained abscesses, as opposed to 1 of 12 for the control lambs. Both polyclonal and antigen-specific IgG concentrations were affected by vitamin A status. Serum cortisol concentrations did not appear to mediate this effect.

Topics: Animals; Antibody Specificity; Body Weight; Female; Hydrocortisone; Immunoglobulin G; Ovalbumin; Random Allocation; Sheep; Sheep Diseases; Vitamin A; Vitamin A Deficiency

Adult rats with experimental vitamin A deficiency and control animals were intraperitoneally injected with chicken ovalbumin (OA) solution and the entrance of native OA into the blood was assessed 3 hours later by competitive radioimmunoassay. The OA amounts circulating in the blood of control animals averaged (0.39 +/- 0.06) X 10(-4)% of the consumed dose, while in the experimental group it averaged (1.33 +/- 0.42) 10(-4)%. Electron microscopy, using colloid lanthanum hydroxide, has shown vitamin A deficiency to give rise to an abrupt reduction in glycocalix layer, as compared to the control, without increasing erythrocyte membrane permeability for tracer particles. It is concluded that vitamin A deficiency leads to a considerable damage of small intestinal permeability for protein macromolecules.

Topics: Animals; Cell Membrane Permeability; Colloids; Intestinal Mucosa; Intestine, Small; Lanthanum; Macromolecular Substances; Microscopy, Electron; Ovalbumin; Rats; Vitamin A Deficiency

Four-day-old pullets fed a vitamin A-deficient diet were stimulated daily with 1 mg 17beta-estradiol-3-benzoate/day for 6 to 19 days. The onset of vitamin A deficiency had no effect on oviduct growth in these chicks; even though vitamin A-deficient chicks showed a severe decline in growth rate while controls (fed the same diet supplemented with retinyl palmitate) continued to grow, estrogen stimulated resulted in similar oviduct size. Ovalbumin concentrations of estrogen-stimulated chicks were determined by immunoprecipitation of the soluble protein supernatant fraction of oviduct. The concentration of ovalbumin in oviducts of chicks fed a vitamin A-supplemented diet was similar in the concentration in oviducts of chicks fed a vitamin A-deficient diet. The incorporation of [3H]glucosamine and 14C-amino acids into immunoprecipitable ovalbumin, following the in vitro incubation of minced oviduct, indicated that ovalbumin synthesis was not affected by vitamin A deficiency. The specific activity of incorporated [3H]glucosamine, the 14C-amino acid incorporation into ovalbumin, the relative rate of ovalbumin synthesis, and the relative effiency of [3H]glucosamine incorporation into ovalbumin were each similar between the two diet groups. The relative efficiency of [3H]glucosamine incorporation into sodium dodecyl sulfate and dithiothreitol extractable membranous proteins of oviduct was not affect by vitamin A deficiency.

Topics: Amino Acids; Animals; Body Weight; Chickens; Electrophoresis, Polyacrylamide Gel; Estradiol; Female; Glucosamine; Organ Size; Ovalbumin; Oviducts; Precipitin Tests; Proteins; Vitamin A Deficiency