Hassan-Zahraee M, Wu J, Gordon J
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Int Immunol. 1998 Nov;10(11):1599-612. doi: 10.1093/intimm/10.11.1599.
This study has shown that T lymphocytes with alphabeta TCR present in normal human skin possess unique characteristics which may allow them to fulfil a unique role in skin. It disclosed that unlike T cells from blood, they are devoid of proliferative capacity in response to any ligand including lectins and phorbol esters, and show a diminished Ca2+ flux in response to phytohemagglutinin (PHA). However, despite this apparent lack of reactivity, these cells respond to stimulation by synthesis of IFN-gamma. Furthermore, this response by T cells from the skin differs from that of T cells in blood in its tempo. Whereas IFN-gamma is first detectable in peripheral blood lymphocytes (PBL) 42 h following stimulation, T cells from skin produce IFN-gamma 2.5 h after activation, or 17 times faster. Whereas synthesis persists in PBL for several days, it only lasts in skin T cells for 90 min. This difference in the kinetics is a consequence of differences in the regulation of IFN-gamma synthesis in PBL and skin-derived T cells. Thus, unlike PBL, T cells in intact unimmunized skin or ex vivo express mRNA for IFN-gamma, transcribed in a constitutive manner. Activation of these cells turns on translation of IFN-gamma synthesis directly and at the same time turns off further transcription of the IFN-gamma gene: cessation of IFN-gamma synthesis coincides with the disappearance of IFN-gamma mRNA within 4 h of activation. These observations suggest that this pre-formed mRNA may be solely responsible for the early synthesis of IFN-gamma in skin, determining both the amount and the duration of its synthesis. We propose that these cells may represent the antigen-specific component of a first-line host defence system in human skin. The reported absence of delayed-type hypersensitivity reactivity in patients with a selective deficit of skin T cells supports this conclusion.
本研究表明，正常人皮肤中存在的具有αβTCR的T淋巴细胞具有独特的特性，这可能使它们在皮肤中发挥独特的作用。研究发现，与血液中的T细胞不同，它们对包括凝集素和佛波酯在内的任何配体均无增殖能力，对植物血凝素（PHA）的反应中Ca2+通量降低。然而，尽管明显缺乏反应性，但这些细胞可通过合成IFN-γ对刺激作出反应。此外，皮肤T细胞的这种反应在时间上与血液中的T细胞不同。外周血淋巴细胞（PBL）在刺激后42小时首次可检测到IFN-γ，而皮肤T细胞在激活后2.5小时产生IFN-γ，速度快17倍。PBL中的合成持续数天，而在皮肤T细胞中仅持续90分钟。动力学上的这种差异是PBL和皮肤来源的T细胞中IFN-γ合成调节差异的结果。因此，与PBL不同，完整未免疫皮肤或离体皮肤中的T细胞以组成性方式转录表达IFN-γ的mRNA。这些细胞的激活直接开启IFN-γ合成的翻译，同时关闭IFN-γ基因的进一步转录：IFN-γ合成的停止与激活后4小时内IFN-γ mRNA的消失同时发生。这些观察结果表明，这种预先形成的mRNA可能是皮肤中IFN-γ早期合成的唯一原因，决定了其合成的量和持续时间。我们认为这些细胞可能代表人类皮肤中一线宿主防御系统的抗原特异性成分。报道的皮肤T细胞选择性缺陷患者缺乏迟发型超敏反应性支持了这一结论。
