Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response

Abstract

Rationale The skin is an important immunological organ which is naturally exposed to a variety of environmental agents including allergens. The current study investigated the systemic effects of epicutaneous exposure to high molecular-weight proteins and allergens. Methods Ear skin of BALB/c mice was gently abraded with adhesive tape prior to application of peanut protein or ovalbumin. Immunity was investigated by studying specific T cell proliferation, cytokine secretion and immunoglobulin production. Epicutaneous immunization was compared to subcutaneous immunization. Skin immunity was explored by studying Langerhans cell (LC) maturation and migration. Results Abrasion of the skin allows potent epicutaneous immunization to protein antigens. High levels of antigen-specific IL-4, IgE and IgG1 with no IgG2a showed that the responses are strongly Th2 biased. Subcutaneous immunization was less potent and gave predominantly Th1 responses. Primary epicutaneous immunization changed responses elicited by subcutaneous antigen in complete Freunds adjuvant from Th1 to Th2. Additionally, epicutaneous immunization converted an existing antigen-specific Th1 response to a Th2 response, indicating dominance of the skin-induced immunity. Abrasion of the skin increased expression of MHC class II, CD86, CD40, CD54 and CD11c on LCs but did not cause migration. Rapid migration from epidermis to draining lymph node was observed only after skin abrasion and exposure to antigen, suggesting that maturation and migration of LCs are independently regulated events. Conclusions These results suggest that protein antigen presentation by LCs favors Th2 responses. This may provide an explanation for allergic sensitization to some antigens. It may also be a useful non-invasive, non-adjuvant-dependent method of vaccination.