Ontogeny of T cells in skin : extrathymic development

在这项研究中，我们鉴定了一种新的真皮thy-1+树突状细胞（真皮thy-1 ^+DC），并进一步研究了1)T细胞在皮肤中的个体发生，2)胎儿角质形成细胞（KC）的细胞因子分泌，3)KC与朗格汉斯细胞（LC）的相互作用。真皮Thy-1^+DC是在小鼠真皮中发现的新型T细胞。其中部分细胞表达gammadeltaTCR和Vgamma3TCR。然而，这些细胞似乎是由异质群体组成的。小鼠胎儿皮肤中含有丰富的T细胞，其数量和形态在胎期均呈现动态变化。此外，小鼠胎儿皮肤含有未成熟的巨噬细胞。在IL-7转基因（tg）小鼠皮肤中，皮炎随着年龄的增长而发展。免疫组化研究显示，IL-7 tg小鼠表皮和真皮中含有丰富的α - T细胞和γ - T细胞。此外，T细胞库分析显示它们是异质的。这可能提示在IL-7tg条件下，胎儿皮肤中的T细胞发生分化，并在出生后发生皮肤炎。需要进一步的研究来澄清这一点。对胎儿皮肤的细胞因子谱也进行了研究，发现表皮和真皮层的细胞因子谱不同。KC来源的细胞因子对LC的影响也进行了研究。这些研究表明，胎儿皮肤是胸腺外T细胞发育的一个部位，这可能解释了皮肤中的T细胞恶性肿瘤，如蕈样真菌病和特应性皮炎的发展。

In this study, we identifiled novel dermal thy-1+ dendritic cells (Dermal Thy-1^+DC) and futher studied, 1) the ontogeny of T cells in the skin, 2) cytokine secretion by fetal keratinocytes (KC), 3) interaction between KC and Langerhans cells (LC). Dermal Thy-1^+DC are novel T cells found in murine dermis. Some of these cells expressed gammadeltaTCR and Vgamma3TCR.Howener, these cells seem to be composed of heterogeneous population. Murine fetal skin had abundant T cells and they showed dynamic change during fetal life in number as well as in morphology. Furthermore, murine fetal skin harbored immature macrophages. In the skin of IL-7 transgenic (tg) mice, dermatits developed with age. Immunohistohemical study of IL-7 tg mice revealed that epidermis and dermis harbored abundant alphabeta T cells and gammadelta T cells. Moreover, T cell repertoire analysis revealed these are heterogeneous. This may suggest that T cells in fetal skin differentiate in IL-7tg condition, and developed dermatitis in tg skin after birth. Further studies are needed to clarify this. Cytokine profiles of fetal skin was also stuied, and different profile between epidermis and dermis was found. The effect of KC derived cytokines on LC was also examined. From these studies, it is suggeted that fetal skin is a site of extrathymic T cell development, and that this may explain the T cell malignancy in the skin such as mycosis fungoides and the development of atopic dermatits.