title: Different profile of CD8+ effector T cells induced in Der p 1-allergic and naïve mice by DNA vaccination.
abstract: DNA vaccination holds great promise in both prophylactic and therapeutic vaccines. Recent evidence suggests that DNA vaccines could be powerful therapies countering Th2-mediated disorders such as allergies. Here, we studied the allergen-specific CD4+ and CD8+ T cell populations induced following immunization of allergic and non-allergic mice with DNA vaccine vectors encoding discrete epitopes of the house dust mite (HDM) Dermatophagoides pteronyssinus group I (Der p 1) allergen. Specifically, mice were sensitized to Der p 1 and exhibited a strong Th2/allergic response. Sensitized and non-allergic mice were then compared for their responses to DNA immunization. Using Elispot analysis, we demonstrate that allergic/vaccinated mice generate a mixed Th1/Th2 response against the allergen with high numbers of allergen-specific CD4+ T cells secreting IFN-gamma or IL-4, whereas in non-allergic/vaccinated mice a polarized Th1 response was dominant. Allergen-specific CD8+ T cells secreting IFN-gamma were induced at equal frequencies in both allergic and non-allergic mice. However, the CD8+ T cells from allergic mice were markedly deficient in their cytotoxic potential when compared to their counterparts in non-allergic mice. These results indicate that during an ongoing Th2 response, DNA vaccination leads to the generation of a distinct population of non-cytotoxic/regulatory CD8+ T cells.
authors.affiliation: Chiron S.p.A., Siena, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Draghi
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jarman
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli-Stampino
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Valiante
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D060829:Arthropod Proteins; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003546:Cysteine Endopeptidases; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D000939:Epitopes; D019444:Vaccines, DNA; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1