Sugaya M, Nakamura K, Tamaki K
Department of Dermatology, University of Tokyo, Japan.
J Invest Dermatol. 1999 Sep;113(3):350-4. doi: 10.1046/j.1523-1747.1999.00697.x.
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.
一种独特的γδT细胞亚群，称为树突状表皮T细胞，存在于小鼠表皮中。此前有报道称，新鲜分离的树突状表皮T细胞和树突状表皮T细胞系表达干扰素-γ的mRNA。最近的研究表明，白细胞介素-18是一种能强烈诱导T细胞产生干扰素-γ的新型细胞因子，由小鼠角质形成细胞和朗格汉斯细胞产生。白细胞介素-12被认为是Th1型辅助性克隆反应的关键细胞因子，也有报道称这些细胞在小鼠皮肤中产生该因子。在本研究中，我们通过酶联免疫吸附测定法证明，在短期培养中，白细胞介素-18和白细胞介素-12协同上调树突状表皮T细胞产生干扰素-γ。C57/BL6小鼠和BALB/C小鼠均是如此，尽管两种小鼠品系产生的干扰素-γ量有所不同。单独的白细胞介素-18或白细胞介素-12均不能诱导树突状表皮T细胞产生干扰素-γ。通过半定量逆转录-聚合酶链反应法在新鲜分离的树突状表皮T细胞中仅微弱检测到干扰素-γmRNA，在用白细胞介素-18和白细胞介素-12刺激12小时后，mRNA表达大幅增加。我们还通过显示小鼠角质形成细胞系Pam 212上主要组织相容性复合体II类表达上调，证实了树突状表皮T细胞产生的干扰素-γ的生物学活性。因此，本研究表明，角质形成细胞和朗格汉斯细胞产生的白细胞介素-18和白细胞介素-12调节树突状表皮T细胞产生干扰素-γ，因此可能在皮肤相关淋巴组织的免疫反应调节中发挥重要作用。
