title: Epidermal dendritic cells induce potent antigen-specific CTL-mediated immunity.
abstract: Professional antigen-presenting cells (APCs) are required for the initiation of an immune response. Dendritic cells (DCs) are the most potent APCs identified thus far and can present antigen in the context of co-stimulatory signals required for the stimulation of both primed and naïve T cells. Cytotoxic T lymphocytes (CTLs) are critical to the immune response against tumors or virally infected cells. Optimal stimulation of antigen-specific CTLs is the goal of evolving immunization strategies for the prevention or therapy of viral infections and tumors. Epidermal dendritic cells (eDCs), or Langerhans cells, can present antigens for the stimulation of CD4+ T cell dependent anti-tumor immunity and may play a role in tumor surveillance. The capacity of eDCs to induce tumor-specific CD8+ CTL immunity has not been determined. We have previously shown that DCs derived from bone marrow precursors (BmDCs) under the influence of cytokines can induce protective, antigen-specific CTL-mediated anti-tumor immunity. Here we show that subcutaneous immunization with ovalbumin (OVA) peptide (SIINFEKL(257-264))-pulsed eDCs induced OVA-specific, CD8+ CTLs that lyse the OVA-expressing target. Furthermore, mice vaccinated with OVA peptide-pulsed eDCs were completely protected from subsequent challenge by the OVA-expressing melanoma MO5. The capacity of peptide-pulsed eDCs to induce CTL-mediated immunity is directly dependent on the dose of eDCs administered. Importantly, the APC capacity of eDCs is comparable to that of BmDCs, as mice immunized with eDC populations containing at least as many class II+/B7.2+ cells as populations of BmDCs were equally protected against challenge with MO5. These results demonstrate that eDCs can be potent inducers of antigen-specific CD8+ CTL-mediated immunity. They suggest that eDCs may be important targets for antigen delivery strategies aimed at inducing antiviral or anti-tumor immunity.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Celluzzi
authors.forename: L D
authors.initials: LD
authors.lastname: Falo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D000939:Epitopes; D005260:Female; D015395:Histocompatibility Antigens Class I; D007111:Immunity, Cellular; D007116:Immunization, Passive; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D010047:Ovalbumin / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010047:Ovalbumin