Ontogeny of T cells in skin : extrathymic development

在本研究中，我们鉴定了一种新的真皮Thy-1+树突状细胞(Dermal Thy-1^+DC)，并进一步研究了1)皮肤T细胞的个体发育，2)胎儿角质形成细胞(KC)分泌细胞因子，3)KC与朗格汉斯细胞(LC)相互作用。真皮Thy-1^+DC是在小鼠真皮中发现的一种新型T细胞。其中部分细胞表达GammaeltaTCR和VGamma3TCR，但这些细胞似乎是由异质性群体组成。小鼠胎儿皮肤中含有丰富的T细胞，在胚胎发育过程中，T细胞在数量和形态上呈现动态变化。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)小鼠的皮肤中，皮炎随着年龄的增长而发展。IL-7Tg小鼠的免疫组织化学研究表明，表皮和真皮中含有丰富的Alphabeta T细胞和Gammadelta T细胞。此外，T细胞谱系分析显示，这些细胞是异质性的。提示胎儿皮肤T细胞在IL-7TG条件下分化，出生后在TG皮肤发生皮炎。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，发现表皮和真皮的细胞因子谱不同。同时观察KC来源的细胞因子对LC的影响。这些研究表明，胎儿皮肤是胸腺外T细胞发育的场所，这可能解释了皮肤中T细胞恶性的原因，如真菌样肉芽肿和特应性皮炎的发生。

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.