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CD40 Engagement Enhances Antigen-Presenting Langerhans Cell Priming of IFN--Producing CD4⁺ and CD8⁺ T Cells Independently of IL-12¹

Anton V. Gorbachev^2,* and Robert L. Fairchild^*,,

^* Department of Immunology and Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH 44195; and Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106

The delivery of CD40 signaling to APCs during T cell priming enhances many T cell-mediated immune responses. Although CD40 signaling up-regulates APC production of IL-12, the impact of this increased production on T cell priming is unclear. In this study an IL-12-independent T cell-mediated immune response, contact hypersensitivity (CHS), was used to further investigate the effect of CD40 ligation on the phenotypic development of Ag-specific CD4⁺ and CD8⁺ T cells. Normally, sensitization for CHS responses induces hapten-specific CD4⁺ T cells producing type 2 cytokines and CD8⁺ T cells producing IFN-. Treatment of mice with agonist anti-CD40 mAb during sensitization with the hapten 2,4-dinitrofluorobenzene resulted in CHS responses of increased magnitude and duration. These augmented responses in anti-CD40 Ab-treated mice correlated with increased numbers of hapten-specific CD4⁺ and CD8⁺ T cells producing IFN- in the skin draining lymph nodes. Identical results were observed using IL-12^–/– mice, indicating that CD40 ligation promotes CHS responses and development of IFN--producing CD4⁺ and CD8⁺ T cells in the absence of IL-12. Engagement of CD40 on hapten-presenting Langerhans cells (hpLC) up-regulated the expression of both class I and class II MHC and promoted hpLC migration into the T cell priming site. These results indicate that hpLC stimulated by CD40 ligation use a mechanism distinct from increased IL-12 production to promote Ag-specific T cell development to IFN--producing cells.

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