Suppression of allergen reactive Th2 mediated responses and pulmonary eosinophilia by intranasal administration of an immunodominant peptide is linked to IL-10 production.
The potential to induce systemic tolerance following exposure of the airway mucosa to soluble antigen, may be applied therapeutically for the treatment of allergic disease. Since the use of allergen can trigger IgE mediated inflammation, we investigated whether mucosal delivery of a peptide, containing an immunodominant epitope of the Der p1 allergen of house dust mite, can lead to CD4(+) Th2 cell tolerance and thus protect against airway inflammatory responses to inhalant allergen. The administration of microencapsulated peptide to the nasal mucosa of mice, protected against airway inflammation, with significant reductions in eosinophil infiltration into the airways following allergen challenge. Der p1 specific antibody levels in sera were not modulated. Allergen reactive CD4(+) T cells expressed a tolerized phenotype, with reduction in levels of the cytokines, IL-5, IL-13 and IFN-gamma although IL-10 levels were increased. The mucosal administration of a peptide containing an immunodominant region of an allergen can protect against the induction of systemic and local inflammatory responses to allergen challenge.
Hall
Gillian
G
Respiratory Medicine Unit, Immunobiology Group, Rayne Laboratory, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
Houghton
Christian G
CG
Rahbek
Janne Uldal
JU
Lamb
Jonathan R
JR
Jarman
Elizabeth R
ER
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D040001:Dermatophagoides farinae / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007958:Leukocyte Count; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D016056:Immunodominant Epitopes; D018793:Interleukin-13; D015848:Interleukin-5; D010455:Peptides; D016753:Interleukin-10; D015847:Interleukin-4