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


CONCLUSIONS
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.
Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Immunology, Nutricia Research, Utrecht, The Netherlands.
Marcel A
MA
Schijf
Joann
J
Kerperien
Jacqueline
J
Bastiaans
Kirsten
K
Szklany
Jenny
J
Meerding
Gerard
G
Hofman
Louis
L
Boon
Femke
F
van Wijk
Johan
J
Garssen
Belinda
B
Van't Land
D000818:Animals; D019587:Dietary Supplements; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006968:Hypersensitivity, Delayed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D020825:T-Box Domain Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D009844:Oligosaccharides; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor