In vivo and in vitro T-cell-activating ability of murine epidermal cells (EC) was investigated in acutely barrier-disrupted skin by extraction of epidermal lipids with acetone or removal of corneocytes by tape stripping. Contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) and picryl chloride (PCl) and contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) were significantly augmented when challenged or sensitized at sites treated with acetone 24 h before, compared with the intact skin. CS to DNFB was also enhanced by tape stripping, but not by water rubbing, suggesting that physical stress or a toxic effect of acetone was not responsible for the augmentation. Semi-quantification of TCSA-EC photoadducts showed markedly increased permeability of hapten in the epidermis 24 h after acetone treatment. Bioactive IL-1alpha was more pronounced in barrier-disrupted than in intact skin. Lymph node T cells from PCl-sensitized mice proliferated significantly more in a hapten-specific and co-stimulatory molecule-dependent manner in response to trinitrophenylated (TNP) EC from acetone-treated skin than to those from untreated skin. Immunofluorescence staining of epidermal sheets and flow cytometric analysis of dispersed EC showed that subpopulations of Langerhans cells (LC) in acetone-rubbed or tape-stripped skin expressed major histocompatibility complex class II CD54 and CD86 molecules at levels higher than the rest of LC and LC from water-treated or untreated epidermis. Therefore, not only increased permeability of hapten through the epidermis but also altered immune functions of EC potentiate T-cell activation in acute barrier disruption. Such augmentation of immune reactivity may be critical to elimination of environmental noxious agents that penetrate easily into the barrier-disrupted epidermis.

H-2K b -restricted tumor epitope peptides, including tyrosinase-related protein 2 residues 181-188 (TRP-2) and connexin 37 residues 52-59 (MUT1), were applied to permeability barrier-disrupted C57BL͞6 (B6) mouse skin from which the stratum corneum of the epidermis had been removed by tape-stripping. This procedure primed tumor-specific cytotoxic T lymphocytes (CTLs) in the lymph nodes and spleen, protected mice against subsequent challenge with corresponding tumor cells, and suppressed the growth of established tumors. Preventive and therapeutic effectiveness was correlated with the frequency of tumor-specific CTL precursors. MHC class II Ia b؉ cells separated from tape-stripped skin, compared with those from intact skin, exhibited a strong antigen-presenting capacity for CTL, suggesting that CTL expansion after peptide application is primarily mediated by epidermal Langerhans cells. Thus, percutaneous peptide immunization via barrier-disrupted skin provides a simple and noninvasive means of inducing potent anti-tumor immunity which may be exploited for cancer immunotherapy. One of the principal goals in tumor immunoprophylaxis and therapy is induction of anti-tumor responses by generating sufficient numbers of tumor antigen-specific cytotoxic T lymphocytes (CTLs). In tumor bearers, however, not only effective CTL priming but also recognition and effective lysis of tumor cells by CTLs are often blocked or attenuated by down-regulated expression of major histocompatibility complex (MHC) class I antigens and of costimulatory and adhesion molecules on tumorcell surfaces (1), suggesting one evasion mechanism of tumor cells which affects immune surveillance. Therefore, establishment of efficient CTL priming strategies is an important issue for cancer immunotherapy.Dendritic cells are potent antigen-presenting cells distributed widely at epithelial surfaces which interface with the external environment to facilitate efficient antigen trapping (2, 3). Because of high levels of expression of MHC class I antigen and costimulatory and adhesion molecules, tumor-specific CTLs are efficiently induced with tumor antigen-or peptide-loaded dendritic cells (4-7). Studies in animal models have shown the potential of dendritic cell-based tumor immunotherapy to elicit protective anti-tumor immune responses, and the validity of such an approach has also been confirmed in humans (8-10). While understanding of the mechanism of propagation of dendritic cells under cytokine influence has progressed at a rapid pace, the intricate manipulations required for in vitro preparation of large numbers of dendritic cells in a form appropriate for immunotherapy seem to be a major drawback in current immunotherapeutic strategies.We have reported that disruption of the skin barrier results in not only enhanced permeability but also alterations in the immunoregulatory function of the skin in such a way that epidermal Langerhans cells (LCs) function as vigorous antigen presenters for T-helper cells (11). Various studies have shown that LCs target tumo...

Although quinolone antibacterial agents have both phototoxicity and photoallergenicity, the latter's potency has been poorly investigated compared with the former's. Some of the photoallergic chemicals serve as photohaptens, which lead to T-cell-mediated immune reactions after photobinding to protein by UVA radiation. We examined the photohaptenic potential of fluoroquinolones, including lomefloxacin (LFLX), ciplofloxacin, norfloxacin, ofloxacin, levofloxacin, fleroxacin, enoxacin and sparfloxacin (SPFX). The absorption spectra of the quinolones were altered by UVA irradiation, with an exception of SPFX that seems to be photostable toward UVA. Bovine serum albumin and murine epidermal cells were coupled with these fluoroquinolones other than SPFX by exposure to UVA. Subcutaneous inoculation of fluoroquinolone-photomodified epidermal cells induced and elicited a delayed-type hypersensitivity reaction in mice. However, epidermal cells incubated with LFLX without UVA exposure also induced and elicited a significant hypersensitivity reaction to a lesser degree than LFLX-photomodified epidermal cells. Furthermore, there was cross-reactivity between LFLX-photomodified epidermal cells and simply LFLX-incubated cells. This suggests that cells can be weakly modified with LFLX even in the dark and that UVA irradiation promotes this modification. Our study demonstrated that fluoroquinolones have photohaptenic properties to which their photoallergenicity is probably ascribed.

Our results indicate that there is a positive correlation between the incidence of the characteristic feature at the epidermal-dermal junction and the visual appearance of a pore.