Ontogeny of T cells in skin : extrathymic development

本研究从人皮肤中分离出Thy-1 ^+树突状细胞（Dermal Thy-1^+DC），并进一步研究了Thy-1 ^+ DC在皮肤T细胞发育、角质形成细胞（KC）分泌细胞因子、KC与朗格汉斯细胞（LC）相互作用等方面的作用。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γ δ TCR和V γ 3 TCR，但这些细胞似乎由异质性细胞群组成。胎鼠皮肤T细胞数量丰富，在胎龄内呈动态变化。此外，小鼠胎儿皮肤窝藏未成熟的巨噬细胞。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-7 tg小鼠的免疫组化研究显示表皮和真皮含有丰富的α T细胞和γ δ T细胞。此外，T细胞库分析显示这些是异质的。这可能表明胎儿皮肤中的T细胞在IL-7 tg条件下分化，并且出生后在tg皮肤中发生皮炎。需要进一步的研究来澄清这一点。研究了胎儿皮肤细胞因子的分布，发现表皮和真皮细胞因子的分布存在差异，并探讨了KC细胞因子对LC的影响。从这些研究中，它被证实，胎儿皮肤是胸腺外T细胞发育的一个网站，这可能解释T细胞恶性肿瘤的皮肤，如蕈样肉芽肿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.