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Limited Ability of Antigen-Specific Th1 Responses to Inhibit Th2 Cell Development In Vivo¹

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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 CD8⁺ DCs induced a Th1 response and the production of IgG2a, whereas CD8^– 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 CD8^– DC transfer, CD8⁺ DCs failed to prime Th1 cells. In contrast, CD8^– 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 CD8⁺ DCs in vitro, but the addition of IFN- did not effectively inhibit the potential of CD8^– 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.

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