Neuber Karsten, Schmidt Saskia, Mensch Andrea
Department of Dermatology, University Hospital Hamburg-Eppendorf, Germany.
Immunology. 2003 May;109(1):24-31. doi: 10.1046/j.1365-2567.2003.01640.x.
The purpose of this study was to investigate the immunosenescence of skin-homing T cells expressing the cutaneous lymphocyte antigen (CLA). Peripheral blood lymphocytes from 72 healthy individuals (33 male and 39 female; median age 54 years; age-range: 18-94 years) were investigated. The expression of CD28, CD45RA and CD45RO, as well as intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) formation of CLA+ 'skin homing' T cells, was analysed. In addition, T cells were detected immunohistologically in skin specimens from 15 young and 15 old, healthy individuals. The relative telomere length (RTL) was measured by fluorescence in situ hybridization using flow cytometry (flow FISH). The total number of CLA+ T cells was found to remain constant with increasing age. In contrast to peripheral blood T cells (CD3+ CLA-), which showed significantly decreased CD28 and CD45RA expression in donors > 60 years of age, no age-related alterations of either CD28+ CLA+ T cells or CD45RA+ CLA+ T cells were observed. In the group of donors > 60 years of age, the proportion of intracellular IFN-gamma-producing CD3+ CLA- cells showed a significant increase, whereas the number of IFN-gamma- and IL-4-producing CLA+ T cells was not affected by age. After stimulation with phytohaemagglutinin (PHA) or staphylococcal enterotoxin B (SEB), CLA+ T cells from old donors did not show a reduced response compared with CLA+ T cells from young donors. Additionally, the counts of T cells in healthy skin from young and old adults were statistically not different. Furthermore, the RTL was significantly shortened in enriched CD45RO+ CLA- T cells from healthy old individuals, but not in aged CLA+ T cells. The present data suggest that CLA+ T cells might be a T-cell subpopulation which does not undergo immunosenescence. This may explain why the intensity of inflammatory skin reactions (e.g. psoriasis or eczema) seems to be independent of the patients' age.
本研究的目的是调查表达皮肤淋巴细胞抗原(CLA)的皮肤归巢T细胞的免疫衰老情况。对72名健康个体(33名男性和39名女性;年龄中位数54岁;年龄范围:18 - 94岁)的外周血淋巴细胞进行了研究。分析了CLA + “皮肤归巢”T细胞中CD28、CD45RA和CD45RO的表达,以及细胞内干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)的形成。此外,对15名年轻和15名老年健康个体的皮肤标本进行了免疫组织化学检测T细胞。使用流式细胞术荧光原位杂交(流式FISH)测量相对端粒长度(RTL)。发现CLA + T细胞的总数随着年龄增长保持不变。与外周血T细胞(CD3 + CLA - )不同,60岁以上供体的外周血T细胞CD28和CD45RA表达显著降低,而未观察到CD28 + CLA + T细胞或CD45RA + CLA + T细胞有与年龄相关的改变。在60岁以上供体组中,产生细胞内IFN-γ的CD3 + CLA - 细胞比例显著增加,而产生IFN-γ和IL-4的CLA + T细胞数量不受年龄影响。用植物血凝素(PHA)或葡萄球菌肠毒素B(SEB)刺激后,老年供体的CLA + T细胞与年轻供体的CLA + T细胞相比,未显示出反应降低。此外,年轻人和老年人健康皮肤中的T细胞计数在统计学上没有差异。此外,健康老年个体富集的CD45RO + CLA - T细胞中的RTL显著缩短,但老年CLA + T细胞中未缩短。目前的数据表明CLA + T细胞可能是一个未经历免疫衰老的T细胞亚群。这可能解释了为什么炎症性皮肤反应(如银屑病或湿疹)的强度似乎与患者年龄无关。