title: Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming.
abstract: We have previously shown that T helper type 2 (Th2)-polarized airway inflammation can facilitate priming to new antigens in the lungs, which we called "collateral priming". To investigate whether allergic skin inflammation can also facilitate priming toward new antigens, we developed an allergic skin inflammation model based on an allergic lung inflammation model. Mice were sensitized intraperitoneally toward the primary antigen, ovalbumin. Challenge was subsequently performed intranasally or epicutaneously with ovalbumin and a secondary antigen, keyhole limpet hemocyanin (KLH). Re-challenge consisted of local application of either antigen alone. Analysis of KLH-specific antibody responses, KLH-specific cytokines, and local inflammation demonstrated tolerance induction toward the secondary antigen in the skin, whereas in the lung priming had occurred. Flow-cytometric analysis revealed increased numbers of regulatory T cells (Tregs), increased cytotoxic T lymphocyte antigen-4 (CTLA-4) expression, and an enhanced suppressive capacity of Tregs from skin-draining lymph nodes when compared with Tregs from the lung-draining lymph nodes. Furthermore, depletion of Tregs resulted in restoration of collateral priming in the skin. These results demonstrate crucial local differences between the Treg function in the skin and lung to repetitive antigen exposure, which can decisively influence the immune response toward new antigens.
authors.affiliation: Department for Pediatric Pulmonology, Allergology and Neonatology, Medical School Hannover, Hannover, Germany.
authors.forename: Subhashree
authors.initials: S
authors.lastname: Mahapatra
authors.affiliation: Department for Pediatric Pulmonology, Allergology and Neonatology, Medical School Hannover, Hannover, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Albrecht
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
authors.forename: Abdul M
authors.initials: AM
authors.lastname: Baru
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Herrick
authors.affiliation: Department for Pediatric Pulmonology, Allergology and Neonatology, Medical School Hannover, Hannover, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Dittrich
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003872:Dermatitis / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007114:Immunization / Q000379:methods*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D011897:Random Allocation; D012867:Skin / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D010047:Ovalbumin