title: Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells.
abstract: Allergic asthma is a chronic inflammatory disease and despite the introduction of potent and effective drugs, the prevalence has increased substantially over the past few decades. The explanation that has attracted the most attention is the 'hygiene hypothesis', which suggests that the increase in allergic diseases is caused by a cleaner environment and fewer childhood infections. Indeed, certain mycobacterial strains can cause a shift from T-helper cell 2 (Th2) to Th1 immune responses, which may subsequently prevent the development of allergy in mice. Although the reconstitution of the balance between Th1 and Th2 is an attractive theory, it is unlikely to explain the whole story, as autoimmune diseases characterized by Th1 responses can also benefit from treatment with mycobacteria and their prevalence has also increased in parallel to allergies. Here we show that treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension, gives rise to allergen-specific CD4+CD45RB(Lo) regulatory T cells, which confer protection against airway inflammation. This specific inhibition was mediated through interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), as antibodies against IL-10 and TGF-beta completely reversed the inhibitory effect of CD4+CD45RB(Lo) T cells. Thus, regulatory T cells generated by mycobacteria treatment may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases.
authors.affiliation: Novartis Horsham Research Centre, Novartis Pharmaceutical Ltd. Wimblehurst Road, Horsham, UK. claudia.zuany-amorim_fromond@pharma.novartis.com
authors.forename: Claudia
authors.initials: C
authors.lastname: Zuany-Amorim
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Sawicka
authors.forename: Corinne
authors.initials: C
authors.lastname: Manlius
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Laura R
authors.initials: LR
authors.lastname: Brunet
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
authors.forename: Gareth
authors.initials: G
authors.lastname: Bowen
authors.forename: Graham
authors.initials: G
authors.lastname: Rook
authors.forename: Christoph
authors.initials: C
authors.lastname: Walker
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D007378:Interleukins / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007378:Interleukins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D010047:Ovalbumin