Limited Ability of Antigen-Specific Th1 Responses to Inhibit Th2 Cell Development In Vivo

• Published in: The Journal of immunology (1950) 2005-02, Vol.174 (3), p.1325-1331
• Main Authors: Yasumi, Takahiro, Katamura, Kenji, Okafuji, Ikuo, Yoshioka, Takakazu, Meguro, Taka-aki, Nishikomori, Ryuta, Kusunoki, Takashi, Heike, Toshio, Nakahata, Tatsutoshi
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD8 Antigens - biosynthesis; Cell Communication - immunology; Cell Differentiation - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - transplantation; Epitopes, T-Lymphocyte - immunology; Growth Inhibitors - pharmacology; Growth Inhibitors - physiology; Immunoglobulin G - biosynthesis; Immunosuppression; Interferon-gamma - biosynthesis; Interferon-gamma - physiology; Interleukin-4 - biosynthesis; Interleukin-4 - pharmacology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Resting Phase, Cell Cycle - immunology; Spleen - cytology; Spleen - immunology; Spleen - metabolism; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.3.1325

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.