Peralbo Esther, DelaRosa Olga, Gayoso Inmaculada, Pita Maria L, Tarazona Raquel, Solana Rafael
Immunology Unit, Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.
Biogerontology. 2006 Oct-Dec;7(5-6):483-92. doi: 10.1007/s10522-006-9063-5.
Invariant natural killer T (iNKT) cells represent a well-established T cell lineage characterised in humans by TCR consisting of an invariant alpha chain encoded by Valpha24-JalphaQ genes, paired preferentially with a Vbeta11 chain. iNKT cells also share some characteristics with NK cells, such as the expression of the NK-associated receptor CD161 in humans. The T cell immune response is the most dramatically affected by ageing, although age-associated alterations in the phenotype and function of other cells of the immune system have been demonstrated. Despite the importance of iNKT cells in the regulation of the immune response, there are a limited number of studies on the effect of ageing on peripheral blood iNKT cells. Thus, in this work we analyse the effect of ageing on peripheral blood Valpha24(+)Vbeta11(+) iNKT cells by studying their frequency, phenotype and proliferative function in elderly individuals fulfilling the SENIEUR criteria of healthy ageing compared with healthy young donors. Our results demonstrated a significant decrease of the percentage of Valpha24(+)Vbeta11(+) iNKT cells in elderly donors. No significant differences were found in the expression of CD27, CD28, CD45RO, CD45RA(bright), CD161, CD94 and NKG2D on iNKT cells from young and elderly individuals. Proliferation of Valpha24(+)Vbeta11(+) iNKT cells in response to alpha-GalCer and IL2 was analysed by calculating the cumulative population doubling (PD) after 14 days of culture. The PD levels were lower in the elderly indicating that Valpha24(+)Vbeta11(+) iNKT cells from healthy elderly subjects had an impaired proliferative capacity. These results indicate that ageing associates with a significant decline in the percentage and proliferative response of peripheral blood iNKT cells. Given the important immunoregulatory role of iNKT cells, these alterations in their number and function could contribute to the deleterious immune response in the elderly.
不变自然杀伤性T（iNKT）细胞代表一种成熟的T细胞谱系，在人类中其特征为TCR由Vα24-JαQ基因编码的恒定α链组成，优先与Vβ11链配对。iNKT细胞也与自然杀伤细胞（NK细胞）有一些共同特征，比如人类中NK相关受体CD161的表达。T细胞免疫反应受衰老影响最为显著，不过免疫系统其他细胞的表型和功能也出现了与年龄相关的改变。尽管iNKT细胞在免疫反应调节中很重要，但关于衰老对外周血iNKT细胞影响的研究数量有限。因此，在本研究中，我们通过研究符合健康衰老SENIEUR标准的老年人外周血Vα24(+)Vβ11(+) iNKT细胞的频率、表型和增殖功能，分析衰老对外周血iNKT细胞的影响，并与健康年轻供体进行比较。我们的结果表明，老年供体中Vα24(+)Vβ11(+) iNKT细胞的百分比显著降低。在年轻和老年个体的iNKT细胞上，CD27、CD28、CD45RO、CD45RA(bright)、CD161、CD94和NKG2D的表达未发现显著差异。通过计算培养14天后的累积群体倍增（PD）来分析Vα24(+)Vβ11(+) iNKT细胞对α-半乳糖神经酰胺（α-GalCer）和白细胞介素2（IL2）的增殖反应。老年人的PD水平较低，表明健康老年受试者的Vα24(+)Vβ11(+) iNKT细胞增殖能力受损。这些结果表明，衰老与外周血iNKT细胞的百分比和增殖反应显著下降有关。鉴于iNKT细胞重要的免疫调节作用，其数量和功能的这些改变可能导致老年人有害的免疫反应。
