UV radiation of the skin impairs immune responses to
haptens and to
tumor Ags. Transcutaneous immunization (TCI) is an effective method of inducing immune responses to
protein and
peptide Ag. We explore the effect of UV irradiation on TCI. The generation of Ag-specific CTL to OVA
protein, but not class I MHC-restricted OVA
peptide, is inhibited by TCI through UV-irradiated skin. Consequently, the induction of
protein contact hypersensitivity and in vivo Ag-specific CTL activity following OVA
protein immunization is prevented. Application of
haptens to UV-exposed skin induces
hapten-specific tolerance. We demonstrate that application of
protein or class II MHC-restricted OVA
peptide to UV-irradiated skin induces transferable Ag-specific tolerance. This tolerance is mediated by CD4(+)CD25(+) T regulatory (T(reg)) cells. These Ag-specific T(reg) cells inhibit the priming of CTL following
protein immunization in the presence of CpG adjuvant.
IL-10 deficiency is known to prevent
hapten-specific tolerance induction. In this study, we demonstrate, using IL-10-deficient mice and adoptive T cell transfer, that
IL-10 is required for the direct inhibition of CTL priming following immunization through UV-irradiated skin. However,
IL-10 is not required for the induction of T(reg) cells through UV-irradiated skin as IL-10-deficient T(reg) cells are able to mediate tolerance. Rather, host-derived
IL-10 is required for the function of UV-generated T(reg) cells. These experiments indicate that
protein and
peptide TCI through UV-irradiated skin may be used to induce robust Ag-specific tolerance to neo-Ags and that UV-induced T(reg) cells mediate their effects in part through the modulation of
IL-10.