Failure of carcinogen-altered dendritic cells to initiate T cell proliferation is associated with reduced IL-1 beta...

The activation of T cells through presentation of antigen by dendritic cells (DC) relies on many factors, including the correct balance of cytokines in the immediate microenvironment. Antigen presentation by DC migrating from carcinogen-treated skin is impaired as evidenced by the failure of antigen-pulsed DC to initiate specific T cell proliferation. To elucidate mechanism(s) of DC dysfunction, DC migrating from carcinogen-treated skin were collected, pulsed with OVA, and cultured with antigen-specific autologous lymphocytes. Supernatants were assayed for the costimulatory cytokine IL-1 beta which influences the outcome of DC:T cell interactions. The dendritic cells migrating from carcinogen-treated skin that failed to induce T cell proliferation were unable to produce IL-1 beta. This may account for the abrogation of DC function following exposure to chemical carcinogens and provides an explanation for the inability of DC to induce a protective immune response to carcinogen-induced tumours.