Changes in epidermal Langerhans cells, gamma delta T cells and CD4 T cells after intradermal infection with recombinant vaccinia virus expressing cytokine genes.

Abstract

Langerhans cells (LC) play a critical role in cutaneous immunity, and whereas Thy-1+ dendritic epidermal cells (Thy-1+ dEC) are also present in murine epidermis, their role remains unknown. Antigens and cytokines influence the number of LC found in the epidermis. However, there has been no investigation into the effects of particular cytokines during resolution of a viral infection. In order to study this we infected mice subcutaneously with vaccinia virus (VV) constructs containing the genes encoding TNF-alpha, IL-6 or IFN-gamma and the density of LC, THY-1+ dEC and CD4+ cells was determined. In this system the cytokines were produced locally at the site of viral replication. Cell densities were examined at day 1, while the response was being initiated, and at day 5 as the infection was being resolved. Infection with VV, like exposure to other antigens, decreased the density of epidermal LC at day 1, and they remained depressed at day 5. Production of TNF-alpha during VV growth did not influence this response by LC, whereas IFN-gamma and IL-6 both increased the number of epidermal Ia+ LC at day 1 but then caused a reduction at day 5. Thy-1+ dEC were not affected by VV infection at any time-point examined, nor did any cytokine influence the density of these cells at day 1. However, by day 5 IFN-gamma and IL-6, but not TNF-alpha, decreased the number of Thy-1+ dEC.(ABSTRACT TRUNCATED AT 250 WORDS)