Neonatal exposure to ultraviolet radiation : implications for development and function of the skin immune system

Exposure to environmental stimuli, including viruses, bacteria and chemicals, during in early life has the capacity to influence the development of disease in adulthood. Presumably exposure to ultraviolet radiation would represent another of these environmental influences. Evidence for this comes from the observation that childhood exposure to sunburning doses of ultraviolet radiation is linked to an increased incidence of melanoma. Recently, laboratory studies have confirmed this relationship, but have been unable to elucidate the mechanism by which melanoma is increased. While numerous studies have demonstrated the significant impact that ultraviolet radiation has on function of the immune system in adults few studies have assessed its effects during the dynamic developmental state of the neonate. This thesis examines the short and long term effects of ultraviolet radiation on the development and function of the neonatal skin immune system. Initial experiments demonstrated a significant alteration in development of the Langerhans cell network of mice following one single exposure to ultraviolet B radiation. In addition, Langerhans cell function was altered, with a consequent skew in immunity away from the cell-mediated response required for tumour immunity. As such, this area warranted further study. A second model was devised in which Cleo Natural lamps emitting solar simulated ultraviolet radiation were utilised. One single exposure to the radiation from these lamps resulted in an arrest in Langerhans cell network development, despite a completely absent inflammatory response. When the contact hypersensitivity response was assessed eight weeks after exposure, there was a significant reduction in the ability to induce an effective response in mice irradiated as neonates. As such, exposure to either ultraviolet B radiation, or solar simulated ultraviolet radiation have the capacity to alter development of the immune response in mice. Remaining experiments focussed on identifying the mechanism by which the immune response was altered. Phenotypic studies identified an altered balance of lymph node cells in irradiated mice, with an increase in the number of T regulatory cells and altered B cell subsets. Functional studies suggested that these T regulatory cells were not the classical ultraviolet radiation induced T regulatory cells, but instead were likely to represent natural T regulatory cells. Results from this thesis have demonstrated a significant alteration in the structure and function of the immune system of mice, following one single exposure to ultraviolet radiation. This contributes to the existing literature, confirming the importance of the neonatal period in establishing immune function in adult life.