Larbi Anis, Douziech Nadine, Dupuis Gilles, Khalil Abdelouahed, Pelletier Hugues, Guerard Karl-Philippe, Fülöp Tamàs
Research Center on Aging, Geriatric Institute, Clinical Research Center, University of Sherbrooke, 1036 Belvedere St. South, Sherbrooke, QC, Canada J1H 4C4.
J Leukoc Biol. 2004 Feb;75(2):373-81. doi: 10.1189/jlb.0703319. Epub 2003 Dec 4.
Aging is associated with a decline in T cell activation and proliferation, but the underlying mechanisms are not fully understood. Recent findings suggest that lipid rafts act as a platform in the initiation of T cell activation by selectively recruiting signaling proteins associated with formation of the initial complex of signal transduction. We tested the hypothesis that lipid raft properties are altered in T lymphocytes from elderly, healthy individuals in comparison with young subjects. Results showed that the cholesterol content of lipid rafts derived from these cells was consistently higher in the case of elderly donors and that membrane fluidity was decreased. In addition, lipid rafts coalescence to the site of T cell receptor engagement was impaired in T cells from elderly donors. The recruitment of p56(lck), linker of activated T cells, and their tyrosine-phosphorylated forms to lipid rafts was decreased in activated T cells from aged individuals. CD45 was not recruited to the lipid raft fractions in either group of subjects. Our data suggest that some properties of lipid rafts are altered in aging, and this finding may be part of the causes for the decline in T cell functions that are observed in elderly individuals.
衰老与T细胞活化和增殖能力下降有关，但其潜在机制尚未完全明确。最近的研究结果表明，脂筏通过选择性募集与信号转导初始复合物形成相关的信号蛋白，在T细胞活化起始过程中充当一个平台。我们检验了这样一个假说：与年轻受试者相比，健康老年人T淋巴细胞中的脂筏特性发生了改变。结果显示，来自这些细胞的脂筏中胆固醇含量在老年供体中始终较高，且膜流动性降低。此外，老年供体的T细胞中脂筏向T细胞受体结合位点的聚集受到损害。在老年个体活化的T细胞中，p56(lck)（活化T细胞连接蛋白）及其酪氨酸磷酸化形式向脂筏的募集减少。在两组受试者中，CD45均未被募集到脂筏组分中。我们的数据表明，衰老过程中脂筏的某些特性发生了改变，这一发现可能是老年个体中观察到的T细胞功能下降的部分原因。
