THE INFLUENCE OF ULTRA VIOLET RADIATION AND OTHER PHYSICAL AND CHEMICAL AGENTS ON EPIDERMAL LANGERHANS CELLS

254Our understanding of the role played by epidermis in systemic immunity has been expanded in recent years from that of a passive cutaneous-environmental interface in which immunologie processes take place to an actively participating organ that initiates and regulates immunologie events. To a large extent, this expanded concept of epidermal immunity has been the result of several observations pertaining to epidermal Langerhans cells (LC), their antigen presenting function, and the perturbation of this function by the different exogenous insults that impinge upon cutaneous immunity. The best studied of these interactions has been the influence of ultraviolet (UV) B radiation on contact hypersensitivity (CH). In the “low-dose” model of this experimental system, local suppression of CH responses in vivo is associated with alterations in the morphology and the antigen presenting function of LC in the irradiated and hapten-painted skin and the appearance of hapten-specific T suppressor (Ts) cells in lymphoid organs. Recent evidence has also indicated that a single exposure to low-dose UVB radiation in vitro can convert the function of intravenously infused, hapten-derivatized LC from induction to down-regulation of CH. Thy-1⁺ epidermal cells (EC) and I-J restricted, Ia⁺ EC in mice, as well as T67DR⁺ cells that immigrate into epidermis in humans, have also been implicated as cellular sources of low-dose UVB-induced immunosuppression. Genetic factors play a major role in low-dose UVB-induced immunosuppression, as judged by the susceptibility or resistance of different strains of mice. In susceptible strains, the induction of CH appears to be dependent on normal numbers of LC, whereas in resistant strains, non-LC dependent mechanisms appear to permit sensitization. The UVB-susceptible trait also appears to be transmitted as an autosomal dominant trait that is regulated in part by the major histocompatibility complex (MHC) genes. Like low-dose UVB radiation, UVA radiation, and psoralens combined with UVA (PUVA) are capable of inducing phenotypic alterations in LC, while preserving their ultrastructure. By contrast, ionizing forms of radiation are reported to produce actual destruction of these antigen presenting cells. Chemical agents also alter the biology of LC. The reactive haptens, dinitrofluorobenzene (DNFB) and trinitrochlorobenzene (TNCB), have been utilized extensively as contact sensitizers. Sensitization to these haptens is associated with the activation of receptor-mediated endocytosis-associated organelles within LC. Polyaromatic hydrocarbons, such as dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene, can also act as contact sensitizers. Skin painting with DNFB, DMBA, or tetradecanoylphorbol 13-acetate (TPA), has been shown to cause suppression of CH to a second sensitizer that is painted soon thereafter. The tolerance induced in this chemical model parallels strikingly the immunosuppression evoked by low-dose UVB, since this unresponsiveness is associated with the depletion of ATPase⁺ LC in locally treated epidermis and with the generation of antigen-specific Ts in systemic circulation. Glucocorticoids, when applied topically or administered systemically, lead to a marked reduction in the density of epidermal LC. On the other hand, investigation of the effect of retinoids on LC has been characterized by discrepant results. Finally, cellophane tape stripping and grafting of cornea and skin have been utilized to demonstrate that LC are the principal source of MHC class II (or la) immunogenicity in skin. These studies have also identified la molecules on LC in combination with hapten to comprise the immunogenic signal for hypersensitivity responses to conventional contact sensitizers.