IL-12 augments CD8(+) T cell development for contact hypersensitivity responses and circumvents anti-CD154 antibody-mediated inhibition

During sensitization with dinitrofluorobenzene for contact hypersensitivity (CHS) responses, hapten-specific CD8(+) T cells develop into IFN-gamma -pr oducing cells, and CD4(+) T cells develop into IL-4/IL-5-producing cells. A dministration of IL-12 during sensitization skews CD4(+) T cell development to IFN-T-producing cells, resulting in exaggerated CHS responses. In the c urrent report we tested the role of IL-12 on CD8(+) T cell development duri ng sensitization and elicitation of CHS to dinitrofluorobenzene. Administra tion of IL-12 during hapten sensitization induced the expression of IL-12R beta2 on both CD4(+) and CD8(+) T cells, augmented IFN-gamma production by these T cell populations, and increased the magnitude and duration of the C HS response to hapten challenge. CHS responses were virtually identical in wild-type and IL-12 p40(-/-) mice. Since engagement of CD40 on APC may stim ulate IL-12 production, we also tested the role of CD40-CD154 interactions on the development of IFN-gamma -producing CD4(+) and CD8(+) T cells follow ing hapten sensitization. Development of IFN-gamma -producing CD4(+) T cell s during hapten sensitization was absent in wild-type mice treated with ant i-CD154 mAb or in CD154(-/-) mice. In contrast, the absence of CD40-CD154 s ignaling had little or no impact on the development of IFN-gamma -producing CD8(+) T cells. These results demonstrate that the development of hapten-s pecific Th1 effector CD4(+) T cells in CHS requires both CD40-CD154 interac tions and IL-12, whereas the development of IFN-gamma -producing effector C D8(+) T cells can occur independently of these pathways.