Analysis of the mechanism of unresponsiveness produced by haptens painted on skin exposed to low dose ultraviolet radiation.

Abstract

It has been acknowledged for decades that ultraviolet B (UVB) 1 (290-320 nm) radiation may have adverse effects on normal cutaneous processes. Acutely, UVB exposure produces cutaneous erythema and edema (sunburn); chronically, it leads to premature cutaneous aging and to the induction of skin cancer. Recently, UVB radiation has been recognized to alter normal immunologic processes (1). Kripke et al. (2) showed that large doses of UVB delivered chronically to mice will not only induce cutaneous neoplasms but will also create a receptive immunologic milieu in which grafts of such UVB-induced neoplasms will grow. Analysis of the immunologic defects that follow high dose UVB exposure has revealed two features that may be relevant: the generation of suppressor T lymphocytes (3, 4) and the failure of Ia positive spleen cells to present antigens to T lymphocytes (5-7). Extrapolation of these findings from mice to man has been difficult because the large UVB doses employed, 180 kJ/m ~, are as much as 400 times the minimal phototoxic UVB dose (MPD) in untanned Caucasian skin. By contrast, Toews et al. (8) have shown that local in vivo administration of a relatively low UVB dose (0.2 kJ/m ~, corresponding to 1 human MPD daily) for four consecutive days also produced an altered immune response in C57BL/6 mice. When the contact-sensitizing agent DNFB was applied to the UVB-irradiated sites (but not to unirradiated sites) antigen-specific unresponsiveness rather than sensitization ensued. The mechanism(s) by which low doses of UVB radiation produce this unresponsiveness to contact sensitizers is unknown. In this study we show that the same dose of UVB radiation that produces a local alteration in antigen-presenting function of skin also permits suppressor T cells to emerge when hapten is placed on the irradiated site. We propose that these suppressor T cells are responsible at least in part for the hapten-specific unresponsive state.

Calcitonin Gene-Related Peptide Decreases Expression of HLA-DR and CD86 by Human Dendritic Cells and Dampens Dendritic Cell-Driven T Cell-Proliferative Responses Via the Type I Calcitonin Gene-Related Peptide Receptor

“…The cellular mechanisms involved in regulation of CH induction by UV radiation, especially the role of LCs, have been studied (17)(18)(19)27). The potential therapeutic effects of UV radiation in inflammatory disorders, including atopic dermatitis and psoriasis, are also described (28).…”

Dendritic cell activation by danger and antigen‐specific T‐cell signalling

“…Growth of epidermal or monocyte derived DC in IL-10 gives rise to DC that induce antigen-specific anergy in T cells (36). Likewise murine LC treated with TNFa, but without GM-CSF, leads to a similar tolerising DC population (39) (and Koch et al, in preparation) and in vivo, UVB irradiation of skin gives rise to tolerising APC that mediate T cell tolerance through anergy or suppressor cell skewing (40,41).…”

Mast cells and cutaneous malignancies

“…Emerging evidence suggests that mast cells may play a critical role in ultraviolet-B-induced immunosuppression [43][44][45][46] ( Figure 1). In a study involving South Australian and Danish subjects, patients with a history of basal cell carcinoma and melanoma are found to have a significantly higher, genetically predetermined density of dermal mast cells.…”