Dermal CD207-Negative Migratory Dendritic Cells Are Fully Competent to Prime Protective, Skin Homing Cytotoxic T-Lymphocyte Responses

Abstract

Dendritic cells (DCs) are important inducers and regulators of T-cell responses. They are able to activate and modulate the differentiation of CD4 þ and CD8 þ T cells. In the skin, there are at least five phenotypically distinct DC subpopulations that can be distinguished by differential expression of the cell surface markers CD207, CD103, and CD11b. Previous studies have suggested that dermal CD11b À CD207 þ conventional type 1 DCs are indispensable for the priming of a skin homing cytotoxic T-lymphocyte response. However, conventional type 1 DCs are also the only skin DC subset capable of cross-presenting exogenous antigens on major histocompatibility complex class I. Thus, it remained unclear whether for antigens that do not require crosspresentation, such as viruses that infect DCs, other DC subtypes in the skin can contribute to cytotoxic T-lymphocyte priming. To address this question, we used a transgenic mouse model that allows inducible expression and presentation of a model antigen on selected subsets of dermal DCs. We show that for antigens presented via the conventional major histocompatibility complex class I presentation pathway, CD207 e dermal DCs are fully competent to prime a skin homing cytotoxic T-lymphocyte response that is capable of protection against a local virus challenge and gives rise to skin resident memory CD8 þ T cells.

Dithranol as novel co-adjuvant for non-invasive dermal vaccination

“…After demonstrating the superior induction of specific T cell responses by DIVA in the primary immune response phase, we evaluated the biological efficacy of this vaccination scheme in a virus infection model. We chose the vaccinia virus (VV-OVA) model, as we have recently demonstrated that CTL primed by skin DCs are highly effective in protecting against a challenge at a distant site 25 . Female mice were treated as indicated in Fig.…”

“…VV-OVA (2 × 10 6 PFU) infection was performed on day 7 days after TCI by i.p. injection 25 . Briefly, 5 days post infection, ovaries were collected, and homogenates seeded on monolayers of BSC-40 fibroblasts in serial dilutions to determine PFU 48–72 h later.…”

The Dynamics of the Skin’s Immune System

“…Dendritic cells that reside in the dermis are known as dermal dendritic cells (dDCs). In a similar manner to LCs, dDCs migrate to the lymph nodes, and are professional antigen-presenting cells efficient at priming adaptive immune responses [117,118]. It was recently shown that dDCs can induce tolerance to topically applied antigens encountered in the hair follicles [119].…”

Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review

“…Using a contact sensitizer hapten, a protein, and a virus, a generation of TRMs in the skin after repetitive antigenic challenges could be observed [72]. Dendritic cells are also able to prime the creation of TRMs in inflamed murine skin [106]. Another study using a contact protein showed that TRMs as well as their local increase following antigen exposure are important for sufficient control of hypersensitivity responses [43].…”