CHANGES IN EPIDERMAL LANGERHANS CELLS, GAMMA-DELTA T-CELLS AND CD4 T-CELLS AFTER INTRADERMAL INFECTION WITH RECOMBINANT VACCINIA VIRUS EXPRESSING CYTOKINE GENES

Langerhans cells (LC) play a critical role in cutaneous immunity, and whereas Thy-1(+) dendritic epidermal cells (Thy-1(+) dEC) are also pre sent in murine epidermis, their role remains unknown. Antigens and cyt okines influence the number of LC found in the epidermis. However, the re has been no investigation into the effects of particular cytokines during resolution of a viral infection. In order to study this we infe cted mice subcutaneously with vaccinia virus (VV) constructs containin g the genes encoding TNF-alpha, IL-6 or IFN-gamma and the density of L C, THY-1(+) dEC and CD4(+) cells was determined. In this system the cy tokines were produced locally at the site of viral replication. Cell d ensities were examined at day 1, while the response was being initiate d, 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-a lpha during VV growth did not influence this response by LC, whereas I FN-gamma and IL-6 both increased the number of epidermal Ia(+) LC at d ay 1 but then caused a reduction at day 5. Thy-1(+) dEC were not affec ted by VV infection at any time-point examined, nor did any cytokine i nfluence the density of these cells at day 1; However, by day 5 IFN-ga mma and IL-6, but not TNF-alpha, decreased the number of Thy-1(+) dEC. These changes in cell densities are consistent with LC but not Thy-1( +) dEC playing a role in initiation of immunity against VV and a compl ex interplay between cytokines and these cells during the response to VV. CD4(+) T cells were also attracted into the epidermis by IFN-gamma and IL-6 but not by TNF-alpha.