Figure 1. Distinct subsets of myeloid dendritic cells induce distinct types of immune responses.

Human LCs induce potent CTL responses, possibly via IL-15: At least four lines of evidence indicate that LCs are remarkable at inducing CTL responses: 1) LCs loaded with an HLA class I peptide potently induce the proliferation of peptide-specific naïve CD8+ T cells; 2) LCs expand naïve CD8⁺ T cells with high avidity against peptide/HLA-I complex; 3) Naive CD8⁺ T cells primed by LCs express high levels of cytotoxic molecules, such as granzymes A, B, and perforin, and display a high cytotoxicity; and 4) LCs are efficient at cross-presentation of antigens. Human CD14+ dermal DCs induce potent humoral responses via IL-12: When DCs form the complex with T cells and B cells at extrafollicular sites, IL-12 derived from activated DCs promotes B cells to differentiate into ASCs by two different paths: a direct path via DC-B interaction, and an indirect path through induction of IL-21-producing Tfh-like cells. We envision that targeting antigens and activation of distinct mDC subsets, with different specializations, will result in the generation of a broad and long lived immune protection. Thus, the most efficient vaccines might be those that will target both LCs and dermal CD14⁺ DCs thereby allowing the maximal stimulation of cellular and humoral immune responses and the generation of long-term memory protection.