Engwerda C R, Fox B S, Handwerger B S
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland at Baltimore 21201, USA.
J Immunol. 1996 May 15;156(10):3621-30.
We previously have shown that T cell proliferation in response to a primary signal through the CD3 epsilon chain and a costimulatory signal via the CD28 molecule is impaired in healthy, aged mice. To determine whether age-related alterations in cytokine production might explain the reduced proliferative responses of T cells from aged mice, we examined the secretion of the major T cell immunoregulatory cytokines, IFN-gamma, IL-4, and IL-2. Splenic T cells from young (2 to 4 mo) and aged (20 to 26 mo) mice were studied. T cells were stimulated with immobilized anti-CD3 epsilon chain mAb and soluble anti-CD28 mAb for 24 h. T cells from aged mice, when compared with young controls, showed increased IFN-gamma production, no difference in IL-4 production, and decreased IL-2 production. Most IFN-gamma was produced by CD8+ T cells, whereas most IL-2 and IL-4 was produced by CD4+ T cells. Both CD4+ and CD8+ T cells from aged mice produced significantly more IFN-gamma than corresponding cells from young mice. This increased production could be accounted for by increased numbers of CD4+CD44high and CD8+CD44high T cells in aged animals. CD4+CD44high and CD8+CD44high T cells from young mice produced comparable amounts of IFN-gamma as corresponding cells from aged mice. In contrast to unseparated splenic T cells, no age-related difference in IL-2 or IL-4 production by purified CD4+ T cells was observed. Similarly, when CD4+ T cells were further separated into CD44low and CD44high subpopulations, no age-related difference in IL-2 production was found. Therefore, we found no consistent evidence that diminished production of the major T cell growth factors, IL-2 and IL-4, is responsible for the age-related decrease in the proliferation of T cell subpopulations that were stimulated in vitro through the CD3 epsilon chain and costimulated via the CD28 molecule. The physiologic relevance of increased IFN-gamma production by T cells from aged mice is unknown.
我们之前已经表明，在健康的老龄小鼠中，T细胞对通过CD3ε链的主要信号以及经由CD28分子的共刺激信号的增殖反应受损。为了确定细胞因子产生方面与年龄相关的改变是否可以解释老龄小鼠T细胞增殖反应的降低，我们检测了主要的T细胞免疫调节细胞因子IFN-γ、IL-4和IL-2的分泌情况。研究了来自年轻（2至4个月）和老龄（20至26个月）小鼠的脾T细胞。用固定化抗CD3ε链单克隆抗体和可溶性抗CD28单克隆抗体刺激T细胞24小时。与年轻对照相比，老龄小鼠的T细胞显示出IFN-γ产生增加，IL-4产生无差异，而IL-2产生减少。大多数IFN-γ由CD8+T细胞产生，而大多数IL-2和IL-4由CD4+T细胞产生。老龄小鼠的CD4+和CD8+T细胞产生的IFN-γ均明显多于年轻小鼠的相应细胞。这种增加的产生可能是由于老龄动物中CD4+CD44high和CD8+CD44high T细胞数量增加所致。年轻小鼠的CD4+CD44high和CD8+CD44high T细胞产生的IFN-γ量与老龄小鼠的相应细胞相当。与未分离的脾T细胞不同，未观察到纯化的CD4+T细胞在IL-2或IL-4产生方面与年龄相关的差异。同样，当将CD4+T细胞进一步分离为CD44low和CD44high亚群时，未发现IL-2产生与年龄相关的差异。因此，我们没有找到一致的证据表明主要T细胞生长因子IL-2和IL-4产生减少是体外通过CD3ε链刺激并经由CD28分子共刺激的T细胞亚群增殖与年龄相关下降的原因。老龄小鼠T细胞产生的IFN-γ增加的生理相关性尚不清楚。
