title: Regulation of Th2 responses and allergic inflammation through bystander activation of CD8+ T lymphocytes in early life.
abstract: Th2-biased immune responses characterizing neonates may influence the later onset of allergic disease. The contribution of regulatory T cell populations in the prevention of Th2-driven pathologies in early life is poorly documented. We investigated the potential of CD8(+) T cells stimulated at birth with alloantigens to modulate the development of allergic airway inflammation. Newborn mice were immunized with semiallogeneic splenocytes or dendritic cells (DCs) and exposed at the adult stage to OVA aeroallergens. DC-immunized animals displayed a strong Th1 and Tc1/Tc2 alloantigen-specific response and were protected against the development of the allergic reaction with reduced airway hyperresponsiveness, mucus production, eosinophilia, allergen-specific IgE and IgG(1), and reduction of lung IL-4, IL-5, IL-10, and IL-13 mRNA levels. By contrast, splenocyte-immunized mice displayed a Th2 and a weak Tc2 alloantigen-specific response and were more sensitive to the development of the allergen-specific inflammation compared with mice unexposed at birth to alloantigens. DC-immunized animals displayed an important increase in the percentage of IFN-gamma-producing CD8(+)CD44(high), CD8(+)CD62L(high), and CD8(+)CD25(+) subsets. Adoptive transfers of CD8(+) T cells from semiallogeneic DC-immunized animals to adult beta(2)m-deficient animals prevented the development of allergic response, in particular IgE, IL-4, and IL-13 mRNA production in an IFN-gamma-dependent manner, whereas transfers of CD8(+) T cells from semiallogeneic splenocyte-immunized mice intensified the lung IL-4 and IL-10 mRNA level and the allergen-specific IgE. These findings demonstrated that neonatal induction of regulatory CD8(+) T cells was able to modulate key parameters of later allergic sensitization in a bystander manner, without recognition of MHC class I molecules.
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Aurore
authors.initials: A
authors.lastname: Dubois
authors.forename: Nathalie
authors.initials: N
authors.lastname: Deruytter
authors.forename: Brigitte
authors.initials: B
authors.lastname: Adams
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delbauve
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fleury
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.forename: Angélique
authors.initials: A
authors.lastname: François
authors.forename: Michel
authors.initials: M
authors.lastname: Pétein
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000097:blood / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D015870:Gene Expression; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin