ovalbumin and Hypercholesterolemia

Recent reports suggest dyslipidemia impairs dendritic cell (DC) function and adaptive immunity. This study aimed to characterize the effect of hypercholesterolemia on antigen-presenting cell function of DCs and DC-dependent CD4(+) T-cell responses. DCs incubated in vitro with acetylated low-density lipoprotein cholesterol with or without an acyl-coenzyme A:cholesterol acyl-transferase inhibitor maintained their ability to prime CD4(+) T cells. Analysis of T-cell proliferation and interferon-gamma and tumor necrosis factor-alpha production after ex vivo coculture of naïve CD4(+) T cells with splenic, inguinal, or iliac DCs from low-density lipoprotein receptor-deficient (LDLR(-/-)) or apolipoprotein E-deficient (ApoE(-/-)) mice fed an atherogenic diet highlighted DC efficacy in effector T-cell generation under hypercholesterolemic conditions. Adoptive transfer of carboxyfluorescein diacetate, succinimidyl ester (CFSE)-labeled naïve CD4(+) T cells in LDLR(-/-) recipients and subsequent immunization demonstrated effective priming of naïve T cells in hypercholesterolemic mice. CFSE dilution analyses revealed that hypercholesterolemic DCs were equipotent in naïve CD4(+) T-cell priming efficacy with normocholesterolemic DCs. Quantitative real-time PCR and flow cytometric analyses demonstrated that DC expression of multiple molecules involved in antigen processing, presentation, and T-cell stimulation remained unaltered by dyslipidemia. Finally, endogenous antigen-primed CD4(+) T cells responded equivalently to a secondary ex vivo antigenic challenge, regardless of whether they were primed in vivo under hypercholesterolemic or control conditions, demonstrating that all essential steps in CD4(+) T-cell responses remain intact under atherogenic conditions. This study affirms that the adaptive immune response prevails under the hypercholesterolemic conditions present in atherosclerosis. In particular, DCs remain functional antigen-presenting cells and maintain their ability to prime CD4(+) T cells even when cholesterol-loaded.

Topics: Adoptive Transfer; Animals; Antigen Presentation; Apolipoproteins E; Atherosclerosis; CD11c Antigen; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Cholesterol, Dietary; Cholesterol, LDL; Coculture Techniques; Dendritic Cells; Disease Models, Animal; Hypercholesterolemia; Interferon-gamma; Lipoproteins, LDL; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Receptors, LDL; Tumor Necrosis Factor-alpha

Humoral and cellular immune responses to several antigens were compared in control and hypercholesterolemic groups of monkeys. Chronic hypercholesterolemia, with concomitant hyperphospholipidemia and hypotriglyceridemia, was produced experimentally by feeding monkeys a high-fat, high-cholesterol diet. When studied prior to infection, hypercholesterolemic monkeys exhibited impaired development of precipitating antibodies against ovalbumin, enhanced sensitivity to tuberculin antigen (stimulated apparently by mycobacterial components in complete Freund adjuvant), and an increased rate of clearance of colloidal carbon from blood. During pneumococcal infection the ability of neutrophiles from hypercholesterolemic monkeys to reduce nitroblue tetrazolium dye showed an increase greater than that of control monkeys; both groups exhibited increased but comparable final clearance rates of colloidal carbon, although the increment of increase was smaller in hypercholesterolemic monkeys.

Topics: Animals; Antibody Formation; Disease Models, Animal; Haplorhini; Hypercholesterolemia; Macaca; Mononuclear Phagocyte System; Ovalbumin; Phospholipids; Pneumococcal Infections; Precipitin Tests; Triglycerides

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cholesterol; Copper; Coronary Disease; Dietary Fats; Dose-Response Relationship, Drug; Hematocrit; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Oils; Ovalbumin; Rats; Species Specificity; Sucrose; Zea mays; Zinc