Schwaiger Susanne, Wolf Anna Maria, Robatscher Peter, Jenewein Brigitte, Grubeck-Loebenstein Beatrix
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
J Immunol. 2003 Jan 1;170(1):613-9. doi: 10.4049/jimmunol.170.1.613.
An increased production of proinflammatory cytokines occurs in a high percentage of elderly persons and is associated with an impaired humoral immune response. However, high IL-4 production has also been observed in old age. We now demonstrate an IL-4-producing subpopulation of CD8+ T cells in a subgroup of healthy older adults. This T cell subset is substantial in size and has a characteristic phenotype expressing CD45RO, CD28, CD62L, and CD25. IL-4-producing CD8+ T cells produce large amounts of IL-2 but not IFN-gamma or perforin, and these cells do not have a regulatory suppressive effect on other T cells. In vivo IL-4-producing CD8+ T cells can be stably detected over a year. When put into culture they also have a stable cytokine production pattern but fail to produce perforin even in the presence of IL-12. This special T cell type does not occur in persons under the age of 40, but is present in 36% of the persons >60 years of age. In this age group, IL-4-producing CD8+ T cells are more frequent in persons who are still capable of raising a humoral immune response following immunization than in others who fail to produce protective Abs after vaccination. Our results suggest that CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults. Due to their phenotype that enables them to migrate into lymphoid tissues and to their capacity to produce IL-4, these cells may counterbalance the overproduction of proinflammatory cytokines in old age.
在很大比例的老年人中促炎细胞因子的产生增加,并且与体液免疫反应受损有关。然而,在老年人群中也观察到高水平的白细胞介素-4(IL-4)产生。我们现在证明,在健康老年成年人的一个亚组中存在产生IL-4的CD8+ T细胞亚群。这个T细胞亚群规模可观,具有表达CD45RO、CD28、CD62L和CD25的特征性表型。产生IL-4的CD8+ T细胞产生大量的IL-2,但不产生干扰素-γ(IFN-γ)或穿孔素,并且这些细胞对其他T细胞没有调节性抑制作用。在体内,产生IL-4的CD8+ T细胞在一年多的时间里都能被稳定检测到。当置于培养中时,它们也有稳定的细胞因子产生模式,但即使在存在白细胞介素-12(IL-12)的情况下也不能产生穿孔素。这种特殊的T细胞类型在40岁以下的人群中不存在,但在60岁以上的人群中有36%存在。在这个年龄组中,在免疫接种后仍有能力产生体液免疫反应的人群中,产生IL-4的CD8+ T细胞比在接种疫苗后不能产生保护性抗体的其他人群中更常见。我们的结果表明,具有CD62L++(明亮)表型的CD8+ T细胞在老年成年人的一个亚组中积累。由于它们的表型使它们能够迁移到淋巴组织中,以及它们产生IL-4的能力,这些细胞可能会抵消老年时促炎细胞因子的过度产生。