IL-12 Augments CD8+ T Cell Development for Contact Hypersensitivity Responses and Circumvents Anti-CD154 Antibody-Mediated Inhibition

Abstract

During sensitization with dinitrofluorobenzene for contact hypersensitivity (CHS) responses, hapten-specific CD8+ T cells develop into IFN-γ-producing cells, and CD4+ T cells develop into IL-4/IL-5-producing cells. Administration of IL-12 during sensitization skews CD4+ T cell development to IFN-γ-producing cells, resulting in exaggerated CHS responses. In the current report we tested the role of IL-12 on CD8+ T cell development during sensitization and elicitation of CHS to dinitrofluorobenzene. Administration of IL-12 during hapten sensitization induced the expression of IL-12Rβ2 on both CD4+ and CD8+ T cells, augmented IFN-γ production by these T cell populations, and increased the magnitude and duration of the CHS response to hapten challenge. CHS responses were virtually identical in wild-type and IL-12 p40−/− mice. Since engagement of CD40 on APC may stimulate IL-12 production, we also tested the role of CD40-CD154 interactions on the development of IFN-γ-producing CD4+ and CD8+ T cells following hapten sensitization. Development of IFN-γ-producing CD4+ T cells during hapten sensitization was absent in wild-type mice treated with anti-CD154 mAb or in CD154−/− mice. In contrast, the absence of CD40-CD154 signaling had little or no impact on the development of IFN-γ-producing CD8+ T cells. These results demonstrate that the development of hapten-specific Th1 effector CD4+ T cells in CHS requires both CD40-CD154 interactions and IL-12, whereas the development of IFN-γ-producing effector CD8+ T cells can occur independently of these pathways.