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

Abstract

The skin is an important immunological organ with an outer protective layer, the stratum corneum forming a barrier between the skin-associated lymphoid tissue and the environment. We show that gently removing the stratum corneum with adhesive tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion by T cells from draining lymph nodes and high levels of specific IgE and IgG1 with no IgG2a showed that the immune responses induced following epicutaneous antigen exposure are strongly Th2 biased. Similar responses were obtained with different antigens and mouse strains. In contrast, subcutaneous immunization with antigen delivery into the dermis was less potent and gave predominantly Th1 responses. Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate. Rapid migration from epidermis to draining lymph node was obtained, however, by exposure to antigen after removal of the stratum corneum, suggesting that maturation and migration of Langerhans cells are independently regulated events. These results suggest that antigen presentation by Langerhans cells gives predominantly 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.

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

“…Our results show robust expression of IFN-g, IL-2 and TNF-a in CD4 1 T cells after immunization with HEL and CT, whereas IL-4 and IL-5 were not detectable, which is in contrast with previous reports that indicated a Th2 cytokine response after ear immunization [10,11]; this also argues against the occurrence of dominant Th2 responses toward antigens that are coadministered with CT in mucosae [16,17]. In the skin, both Th1 and Th2 cytokines have been reported following immunization with OVA and CT [24].…”

“…It has been reported that LCs remain in the epidermis for 48 h, even in the presence of Th1-polarizing adjuvants [7]. In our experiments, 24 h after CT or CTB inoculation in the ear, the number of LCs in the epidermis was reduced, suggesting that LCs could be mobilized from the dermis at this time point in the presence of strong adjuvants such as CT.Our results show robust expression of IFN-g, IL-2 and TNF-a in CD4 1 T cells after immunization with HEL and CT, whereas IL-4 and IL-5 were not detectable, which is in contrast with previous reports that indicated a Th2 cytokine response after ear immunization [10,11]; this also argues against the occurrence of dominant Th2 responses toward antigens that are coadministered with CT in mucosae [16,17]. In the skin, both Th1 and Th2 cytokines have been reported following immunization with OVA and CT [24].…”

“…Several strategies for skin immunization have been developed [10,12,14,24]. However, the nature of the CD4 1 T-cell response that is dominant in the skin and the role of migrating DCs in the presence of different adjuvants in shaping the immune response are important issues that need to be investigated.…”

“…Dermal DCs are also migrating DCs that colonize lymph nodes more rapidly than LCs [6,7], and different roles for skin DC subsets in T-cell priming have been reported [7][8][9]. Skin immunization has yielded controversial data, with some reports supporting a Th2-type response [10,11] and others a Th1-type response [12,13]. IL-17-producing CD4 1 T cells (Th17) have also been found after skin immunization [13,14].…”

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

“…This barrier disruption process is painless, highly effective in augmenting the transfer of macromolecules such as proteins or DNA into skin, and has been successfully utilized in human clinical trials. 46,[48][49][50] An additional advantage is that physical barrier disruption itself has been shown to trigger activation of keratinocytes and LCs in skin, providing some level of 'built-in' adjuvant response. [44][45][46][49][50][51][52] We thus tested a model where the dorsal ears of anesthetized mice were tape-stripped followed by application of as-assembled, airdried (Poly-1/ova) 40 films on either glass or PDMS substrates, fixed in place by surgical tape against the exposed ear skin, mimicking a common strategy used in skin vaccination studies 45,46 (Figure 1a).…”