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老年人中初始(CD45RA+)和记忆(CD45RO+)T淋巴细胞上CD50和CD62L黏附受体的表达

CD50 and CD62L adhesion receptor expression on naive (CD45RA+) and memory (CD45RO+) T lymphocytes in the elderly.

作者信息

De Martinis M, Modesti M, Profeta V F, Tullio M, Loreto M F, Ginaldi L, Quaglino D

机构信息

Department of Internal Medicine and Public Health, University of L'Aquila, Via San Sisto, 22/E, I-67100 L'Aquila, Italy.

出版信息

Pathobiology. 2000;68(6):245-50. doi: 10.1159/000055933.

Abstract

A complex reshaping characterizes cellular immunity in the elderly. In particular, the hallmark of the "senescence" of the T cell compartment is a decrease in the proportion of CD45RA+ naive T lymphocytes concomitantly with an expansion of CD45RO+ memory T cells. However, in addition to age-dependent changes in their representation, phenotypical and functional anomalies also characterize naive and memory T cell populations in the elderly. Since cell adhesion molecules (CAMs) are multifunctional receptors which play important roles not only in cell-to-cell and cell-to-matrix interactions but also in signal transduction and cell activation, we analysed, by means of a three-colour flow cytometry method, the proportion, absolute number and density expression or mean fluorescence intensity (MFI) of CD50 (ICAM-3) and CD62L (L-selectin homing receptor) adhesion receptors on CD45RA+ and CD45RO+ peripheral blood CD3+ T cell subsets from 10 healthy elderly subjects and 10 young controls. Our aim was to investigate age-dependent changes in the expression pattern of these CAMs on naive and memory lymphocytes which might contribute to the remodelling of the immune system in the elderly. We considered the mean values +/- standard deviations of the percentage, absolute number and MFI of positive cells. The percentage of naive T cells expressing CD50 was not significantly modified in aged (94.8 +/- 5.0%) compared to young individuals (97.8 +/- 3.2%). On the contrary, the percentage of memory T cells exhibiting CD50 was lower in elderly than young donors (92.0 +/- 6.4 vs. 98.3 +/- 2.2%; p < 0.01). The percentage of naive T cells expressing CD62L was decreased in the elderly donors (53.3 +/- 18.8 vs. 80.8 +/- 11.0%; p < 0.001), whereas the proportion of CD62L+ memory T lymphocytes was substantially comparable between the two age groups (63.5 +/- 15.7 vs. 54.7 +/- 12.3%). The absolute number per mm(3) of CD50+ naive T cells from aged individuals was decreased (251.9 +/- 141.9 vs. 621.8 +/- 238.0/mm(3); p < 0.001), whereas memory peripheral blood T lymphocytes expressing CD50 were substantially unchanged (863.8 +/- 260.9 vs. 802.7 +/- 139.6/mm(3)). On the contrary, the absolute numbers per mm(3) of naive and memory peripheral blood T lymphocytes exhibiting CD62L were respectively decreased (190.8 +/- 133.4/mm(3)) and increased (515.1 +/- 146.8/mm(3)) in elderly donors compared to young controls (601.3 +/- 129.1 and 351.8 +/- 195.0/mm(3); p < 0.001 and p < 0.05, respectively). Finally, CD50 MFI values of naive as well as memory T cell subpopulations from aged subjects were increased compared to young donors (14.0 +/- 2.0 vs. 9.8 +/- 1.2 and 14.0 +/- 2.0 vs. 11.6 +/- 1.3; p < 0.001 and p < 0.01, respectively). CD62L was also overexpressed in both naive (8.4 +/- 1.6 vs. 6.7 +/- 1.4; p < 0.05) and memory (10.3 +/- 2.5 vs. 5.4 +/- 1.1; p < 0.001) T subsets in the elderly. CD50 and CD62L upregulation could be interpreted as a compensatory mechanism for a decreased responsiveness and a greater requirement for activation signals rather than an age-related anomaly.

摘要

细胞免疫重塑是老年人细胞免疫的一个复杂特征。特别是,T细胞区室“衰老”的标志是CD45RA+初始T淋巴细胞比例下降,同时CD45RO+记忆T细胞扩增。然而,除了其数量随年龄的变化外,老年人的初始和记忆T细胞群体还存在表型和功能异常。由于细胞粘附分子(CAMs)是多功能受体,不仅在细胞间和细胞与基质的相互作用中起重要作用,还参与信号转导和细胞激活,我们采用三色流式细胞术方法,分析了10名健康老年人和10名年轻对照者外周血CD3+T细胞亚群中CD45RA+和CD45RO+上CD50(ICAM-3)和CD62L(L-选择素归巢受体)粘附受体的比例、绝对数量、密度表达或平均荧光强度(MFI)。我们的目的是研究这些CAMs在初始和记忆淋巴细胞上表达模式的年龄依赖性变化,这些变化可能有助于老年人免疫系统的重塑。我们考虑了阳性细胞百分比、绝对数量和MFI的平均值±标准差。与年轻人(97.8±3.2%)相比,老年人中表达CD50的初始T细胞百分比无显著变化(94.8±5.0%)。相反,老年人中表达CD50的记忆T细胞百分比低于年轻供体(92.0±6.4对98.3±2.2%;p<0.01)。老年人供体中表达CD62L的初始T细胞百分比降低(53.3±18.8对80.8±11.0%;p<0.001),而两个年龄组中CD62L+记忆T淋巴细胞的比例基本相当(63.5±15.7对54.7±12.3%)。老年人中每立方毫米CD50+初始T细胞的绝对数量减少(2,51.9±141.9对621.8±238.0/立方毫米;p<0.001),而表达CD50的记忆外周血T淋巴细胞基本无变化(863.8±260.9对802.7±139.6/立方毫米)。相反,与年轻对照者相比,老年人供体中每立方毫米表达CD62L的初始和记忆外周血T淋巴细胞的绝对数量分别减少(190.8±133.4/立方毫米)和增加(515.1±146.8/立方毫米)(分别为601.3±129.1和351.8±195.0/立方毫米;p<0.001和p<0.05)。最后,与年轻供体相比,老年人的初始和记忆T细胞亚群的CD50 MFI值增加(14.0±2.0对9.8±1.2和14.0±2.0对11.6±1.3;p<0.001和p<0.01)。CD62L在老年人的初始(8.4±1.6对6.7±1.4;p<0.05)和记忆(10.3±2.5对5.4±1.1;p<0.001)T亚群中也过表达。CD50和CD62L的上调可解释为反应性降低和对激活信号需求增加的一种补偿机制,而非与年龄相关的异常。

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