Holbrook N J, Chopra R K, McCoy M T, Nagel J E, Powers D C, Adler W H, Schneider E L
Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224.
Cell Immunol. 1989 Apr 15;120(1):1-9. doi: 10.1016/0008-8749(89)90169-x.
Lymphocytes of aged animals exhibit a marked decrease in proliferative capacity in response to mitogen stimulation when compared to those of younger animals. In humans and mice the decreased proliferation is due at least in part (i) to the inability of lymphocytes to synthesize sufficient interleukin 2 (IL-2) and (ii) to decreased expression of IL-2 receptors (IL-2R) on the surface of aged lymphocytes. We compared proliferative abilities, IL-2 production, and IL-2R expression in splenocyte cultures of 4- to 5- and 22- to 24-month-old Fischer 344 rats stimulated with either concanavalin A (Con A) or A23187 and phorbol myristate acetate (PMA). Proliferation was significantly decreased in aged lymphocytes (30-50%) with both treatment protocols. However, unlike mice and humans we observed no difference in IL-2 activity, IL-2 mRNA levels, or IL-2R cell surface expression of lymphocytes from young and aged rats stimulated with either Con A or A23187 and PMA. These results indicate that factors other than decreased expression of IL-2 and IL-2R are responsible for the diminished proliferative capacity of aged rat lymphocytes following mitogen stimulation.
与年轻动物的淋巴细胞相比,老年动物的淋巴细胞在受到丝裂原刺激时,其增殖能力显著下降。在人类和小鼠中,增殖能力下降至少部分是由于:(i)淋巴细胞无法合成足够的白细胞介素2(IL-2);(ii)老年淋巴细胞表面IL-2受体(IL-2R)的表达降低。我们比较了用伴刀豆球蛋白A(Con A)或A23187与佛波酯(PMA)刺激的4至5月龄和22至24月龄Fischer 344大鼠脾细胞培养物中的增殖能力、IL-2产生和IL-2R表达。两种处理方案下,老年淋巴细胞的增殖均显著降低(30 - 50%)。然而,与小鼠和人类不同,我们观察到用Con A或A23187与PMA刺激的年轻和老年大鼠淋巴细胞的IL-2活性、IL-2 mRNA水平或IL-2R细胞表面表达没有差异。这些结果表明,IL-2和IL-2R表达降低以外的因素是丝裂原刺激后老年大鼠淋巴细胞增殖能力减弱的原因。