title: Limited ability of antigen-specific Th1 responses to inhibit Th2 cell development in vivo.
abstract: Th1 and Th2 cells mutually antagonize each other's differentiation. Consequently, allergen-specific Th1 cells are believed to be able to suppress the development of Th2 cells and to prevent the development of atopic disorders. To determine whether a pre-existing Ag-specific Th1 response can affect the development of Th2 cells in vivo, we used an immunization model of Ag-pulsed murine dendritic cell (DC) transfer to induce distinct Th responses. When transferred into naive mice, Ag-pulsed CD8alpha(+) DCs induced a Th1 response and the production of IgG2a, whereas CD8alpha(-) DCs primed a Th2 response and the production of IgE. In the presence of a pre-existing Ag-specific Th2 environment due to Ag-pulsed CD8alpha(-) DC transfer, CD8alpha(+) DCs failed to prime Th1 cells. In contrast, CD8alpha(-) DCs could prime a Th2 response in the presence of a pre-existing Ag-specific Th1 environment. Moreover, exogenous IL-4 abolished the Th1-inducing potential of CD8alpha(+) DCs in vitro, but the addition of IFN-gamma did not effectively inhibit the potential of CD8alpha(-) DCs to prime IL-4-producing cells. Thus, Th1 and Th2 cells differ in their potential to inhibit the development of the other. This suggests that the early induction of allergen-specific Th1 cells before allergy sensitization will not prevent the development of atopic disorders.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Katamura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Okafuji
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Meguro
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusunoki
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma