Interleukins 18 and 12 Synergistically Upregulate Interferon-γ Production by Murine Dendritic Epidermal T Cells

A unique subset of gammadelta T cells, termed dendritic epidermal T cells, reside in murine epidermis. It was previously reported that freshly isolated dendritic epidermal T cells and dendritic epidermal T cell lines expressed mRNA for interferon-gamma. Recent studies indicated that interleukin-18, a novel cytokine which strongly induces interferon-gamma production by T cells, was produced by murine keratinocytes and Langerhans cells. Interleukin-12, which is regarded as a key cytokine for Th1 type helper clone responses, has also been reported to be produced by these cells in murine skin. In this study, we demonstrated by enzyme-linked immunosorbent assay that interleukin-18 and interleukin-12 synergistically upregulated interferon-gamma production by dendritic epidermal T cells in short-term cultures. This was the case in both C57/BL6 mice and BALB/C mice, although the quantity of interferon-gamma produced was different in the two mouse strains. Interleukin-18 or interleukin-12 alone did not induce interferon-gamma production by dendritic epidermal T cells. Interferon-gamma mRNA was only weakly detected by the semiquantitative reverse transcriptase-polymerase chain reaction method in freshly isolated dendritic epidermal T cells, and the mRNA expression was much increased 12 h after stimulation with interleukin-18 and interleukin-12. We also confirmed biologic activity of interferon-gamma produced by dendritic epidermal T cells by showing upregulation of major histocompatibility complex class II expression on Pam 212, murine keratinocyte cell line. Thus, this study suggests that interleukin-18 and interleukin-12 produced by keratinocytes and Langerhans cells regulate interferon-gamma production by dendritic epidermal T cells and thus may play important parts in the regulation of immune responses in skin-associated lymphoid tissues.