title: Tissue localization and frequency of antigen-specific effector CD4 T cells determines the development of allergic airway inflammation.
abstract: Previous activation of effector Th2 cells is central to the development of allergic inflammatory responses. We have observed that priming of allergen-specific Th2 cells in C57BL/6 or B10.A mice with allergen delivered via the i.p. or s.c. routes results in very different outcomes following subsequent airway exposure to the same allergen. Systemic allergen immunization (via the i.p. route) resulted in the formation of a lung-resident population of allergen-specific T cells, and mice developed severe allergic airway inflammation in response to inhaled allergen. The localization of cells to the lung did not require the presence of antigen at this site, but reflected a large pool of circulating activated allergen-specific T cells. In contrast, localized immunization (via the s.c. route) resulted in a small T-cell response restricted to the draining lymph node, and mice were not responsive to inhaled allergen. These data indicate that prior sensitization to an allergen alone was not sufficient for the induction of allergic inflammation; rather, responsiveness was largely determined by precursor frequency and tissue localization of the allergen-specific effector Th2 cells.
authors.affiliation: Malaghan Institute of Medical Research, Wellington School of Medicine, University of Otago, Wellington, New Zealand. nicola.harris@usz.ch
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.forename: John
authors.initials: J
authors.lastname: Holloway
authors.forename: Penny
authors.initials: P
authors.lastname: Fitzharris
authors.forename: Michael
authors.initials: M
authors.lastname: McDonald
authors.forename: Mali
authors.initials: M
authors.lastname: Camberis
authors.forename: Barbara
authors.initials: B
authors.lastname: Fazekas de St Groth
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
authors.forename: Graham
authors.initials: G
authors.lastname: Le Gros
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007114:Immunization; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010047:Ovalbumin