Alterations in regulatory T cells induced by specific oligosaccharides improve vaccine responsiveness in mice

• Published in: PloS one Vol. 8; no. 9; p. e75148
• Main Authors: Schijf, Marcel A, Kerperien, Joann, Bastiaans, Jacqueline, Szklany, Kirsten, Meerding, Jenny, Hofman, Gerard, Boon, Louis, van Wijk, Femke, Garssen, Johan, Van't Land, Belinda
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.09.2013; Public Library of Science (PLoS)
• Subjects: Animals; Breastfeeding & lactation; Carbohydrates; CD25 antigen; CD4 antigen; CD69 antigen; Comparative analysis; CXCR3 protein; Diet; Dietary Supplements; Disease; Flow Cytometry; Foxp3 protein; GATA-3 protein; GATA3 Transcription Factor - metabolism; Homeostasis; Hospitals; Hypersensitivity, Delayed; Immune response; Immunology; Immunomodulation; Immunoregulation; Infections; Inflammation; Influenza; Influenza vaccines; Intervention; Lymph nodes; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; Microbiota; Modulation; Nutrition research; Oligosaccharides; Oligosaccharides - pharmacology; Orthomyxoviridae - drug effects; Orthomyxoviridae - physiology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - prevention & control; Pediatrics; Pharmaceutical sciences; Prebiotics; Respiratory syncytial virus; T cells; T-Box Domain Proteins - metabolism; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; Transcription factors; Vaccination; Vaccines; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075148

Prophylactic vaccinations are generally performed to protect naïve individuals with or without suppressed immune responsiveness. In a mouse model for Influenza vaccinations the specific alterations of CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Tregs) in the immune modulation induced by orally supplied oligosaccharides containing scGOS/lcFOS/pAOS was assessed. This dietary intervention increased vaccine specific DTH responses. In addition, a significant increased percentage of T-bet(+) (Th1) activated CD69(+)CD4(+) T cells (p<0.001) and reduced percentage of Gata-3(+) (Th2) activated CD69(+)CD4(+)T cells (p<0.001) was detected in the mesenteric lymph nodes (MLN) of mice receiving scGOS/lcFOS/pAOS compared to control mice. Although no difference in the number or percentage of Tregs (CD4(+)Foxp3(+)) could be determined after scGOS/lcFOS/pAOS intervention, the percentage of CXCR3 (+) /T-bet(+) (Th1-Tregs) was significantly reduced (p<0.05) in mice receiving scGOS/lcFOS/pAOS as compared to mice receiving placebo diets. Moreover, although no absolute difference in suppressive capacity could be detected, an alteration in cytokine profile suggests a regulatory T cell shift towards a reducing Th1 suppression profile, supporting an improved vaccination response. These data are indicative for improved vaccine responsiveness due to reduced Th1 suppressive capacity in the Treg population of mice fed the oligosaccharide specific diet, showing compartmentalization within the Treg population. The modulation of Tregs to control immune responses provides an additional arm of intervention using alternative strategies possibly leading to the development of improved vaccines.