Epicutaneous immunization with TNP-Ig antigen induces CD11c+IL-10+dendritic cells that promote suppression of Th1-mediated contact hypersensitivity in humanized HLA-DR4 transgenic mice

The contact hypersensitivity response (CHS) is a mouse model of allergic contact dermatitis in humans. The reaction is classified as type IV hypersensitivity and underlies many autoimmune disorders. Experiments employing the CHS model in wild-type mice showed that the protein antigen applied to the skin in the form of a gauze patch one week before the induction of Th1-dependent CHS was an effective strategy to reduce the in-flammatory response in the skin. The approach of epicutaneous (EC) immunization also effectively suppressed the inflammatory response in various mouse models of autoimmune diseases.To evaluate the potential of EC immunization to suppress T cell-dependent immune response in humans, we used HLA-DR4 tg mice, which express the human DRB1*0401 allele and lack all endogenous mouse MHC class II genes.Our data show that EC immunization with TNP-conjugated protein antigen followed by induction of CHS to trinitrochlorobenzene (TNCB), effectively suppressed the CHS response as described by ear swelling, MPO ac-tivity in ear extracts, and the number of TCR beta+CD4+IFN-gamma+ CHS T-effector cells in auxiliary and inguinal lymph nodes (ALN) and spleen (SPL) of HLA-DR4 tg mice. EC-induced suppression increases the frequency of CD11c+IL-10+ DCs in SPL. Their immunoregulatory role was confirmed by s.c. immunization with TNP-CD11c+DCs prior to CHS elicitation and induction.Our data in HLA-DR4 tg mice show that EC protein immunization induces IL-10-producing DCs, which sup-press the development of CD4+IFN-gamma+ T cell-dependent CHS, implying that EC protein immunization could be of therapeutic importance for T cell-mediated diseases in humans.

Automated summary

The contact hypersensitivity response (CHS) is a mouse model that mimics allergic contact dermatitis in humans. Experiments in mice showed that applying a protein antigen to the skin before inducing CHS effectively reduces the inflammatory response. Epicutaneous immunization also suppresses inflammatory response in various mouse models of autoimmune diseases. This suggests that EC immunization could be a therapeutic approach for T cell-mediated diseases in humans.