Ultroviolet B radiation has profound influences on cutaneous immunologic processes. In experimental animals, this ubiquitous environmental agent inhibits immunity to UVB-induced tumors and limits the induction of immunologic reactions to contact sensitizing agents. An inability of epidermal cells and monounclear phagocytes to activate helper T lymphocytes appears to be central to this effect. However, nearly all studies dealing with ultraviolet B photoimmunology have been conducted in animals. Thus, the relevance of these findings to humans is unknown. The objective of this proposal is to characterize the influence of UVB on accessory cell function of epidermal cells and blood monocytes in humans. Human peripheral blood monocytes will be isolated and exposed in vitro to UVB radiation. Irradiated cells will be evaluated for their ability to reconstitue accessory cell dependent in vitro antigen- and mitogen-stimulated assays of T lymphocyte activation. Effects of UVB radiation of specific signals -- antigen processing, interleukin-1 production, HLA-DR antigen expression -- will be evaluated. In vitro assays of epidermal cell accessory function for soluble antigen and mitogens in humans have been developed, and will be employed to examine UVB effects on epidermal cells. T lymphocytes, when co-cultured with UVB-irradiated accessory cells and OKT3, will be studied for their ability to internalize the T cell receptor, elaborate IL-2, and express IL-2 receptors. The accessory cell function of UVB-irradiated monocytes from patients with xeroderma pigmentosum, a disease noted for the development of UV-induced neoplasms at an early age, will be examined for unusual UVB sensitivity. The in vitro studies will be extended to the in vitro situation by exposing healthy human volunteers to UVB radiation and assessing numbers and function of monocyte subpopulations in the blood and skin. Finally, the relationship of UVB-induced alterations in accessory function to the initiation of contact hypersensitivity will be evaluated in a preliminary manner by exposing human volunteers to UVB radiation in vivo and attempting to sensitize them to the contact sensitizer squaric acid dibutyl ester. Knowledge obtained from these studies may help to define the effect of UVB exposure on cutaneous and systemic immunologic processes in humans and enhance our understanding of the role of this environmental agent in the pathogenesis of human disease.
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