Abrogation of Afferent Lymph Dendritic Cell Function after Cutaneously Applied Chemical Carcinogens

Chemical carcinogens reduce cutaneous immunity, an event accompanied by alterations to the number and morphology of the resident epidermal Langerhans cell (LC) population. This study aimed to examine the functional capacity of LC and other dendritic cells (DC) that are migrating from carcinogen-treated skin via afferent lymphatic vessels. Generation and subsequent cannulation of prefemoral pseudoafferent lymphatic vessels in sheep allowed continuous collection of DC migrating from a defined area of carcinogen-treated skin. The ability of metrizamide-enriched afferent lymph DC to present antigen to autologous primed peripheral blood lymphocytes was used as an indicator of DC function. Topical application of the complete carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene abrogated the stimulatory capacity of migrating DC for periods of 8 weeks and 5 weeks, respectively, whereas the tumor promoter 12-O-tetradecanoylphorbol-13-acetate reduced DC function for less than 1 week. These findings favor tumor development in carcinogen-treated skin being enhanced due to impairment of DC immunological surveillance.