Kirschmann D A, Murasko D M
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Cell Immunol. 1992 Feb;139(2):426-37. doi: 10.1016/0008-8749(92)90083-2.
Numerous changes have been reported to occur in T cell responsiveness of mice with increasing age. However, most of these studies have examined polyclonal stimulation of spleen cells from a limited number of mouse strains. This study investigated the influence of genetic background, source of lymphocytes, and type of stimulus on age-associated changes in T cells response. Con A-induced proliferation and IL-2 and IFN-gamma production by splenic lymphocytes (SL) was significantly greater in CBA/Ca mice compared to C57BL/6 mice, regardless of age. SL of both strains exhibited the predicted age-dependent decline in proliferative response and an increase in IFN-gamma production in response to Con A. In contrast, however, only SL from C57BL/6 mice demonstrated the predicted age-dependent decline in Con A-induced IL-2 production; Con A-induced SL of young and aged CBA/Ca mice produced comparable amounts of IL-2. Differences in age-associated responses to Con A were also observed between SL and inguinal lymph node (ILN) cells of CBA/Ca mice. In contrast to SL, ILN cells demonstrated an increased proliferative response to Con A. However, lymphokine production by Con A-stimulated ILN cells from aged CBA/Ca mice was similar to that of Con A-stimulated SL from aged CBA/Ca mice. To determine if aged ILN T cells respond similarly to polyclonal and antigen-specific stimuli, keyhole limpet hemocyanin (KLH) responses of T cells isolated from ILN of aged and young CBA/Ca mice were examined. KLH-specific T cells from aged mice cultured with KLH-pulsed macrophages (M phi) from aged mice were significantly reduced in their ability to proliferate compared to KLH-specific T cells of young mice cultured with young KLH-pulsed M phi. In contrast to the expected results, the defect was not at the level of the T cells; proliferation of young T cells cultured with aged KLH-pulsed M phi was equivalent to the proliferation of aged T cells cultured with aged M phi. These results suggest that aging has differential effects on polyclonal and antigen-specific T cell proliferation and on polyclonal stimulation of T cells isolated from different lymphoid organs and from different strains of mice.
据报道,随着年龄增长,小鼠的T细胞反应性会发生许多变化。然而,这些研究大多检测了有限数量小鼠品系脾细胞的多克隆刺激。本研究调查了遗传背景、淋巴细胞来源和刺激类型对T细胞反应中与年龄相关变化的影响。无论年龄大小,与C57BL/6小鼠相比,CBA/Ca小鼠脾淋巴细胞(SL)对刀豆蛋白A(Con A)诱导的增殖以及白细胞介素-2(IL-2)和干扰素-γ(IFN-γ)的产生显著更高。两种品系的SL均表现出预期的增殖反应随年龄增长而下降,以及对Con A反应中IFN-γ产生增加。然而,相比之下,只有C57BL/6小鼠的SL表现出预期的Con A诱导的IL-2产生随年龄增长而下降;Con A诱导的年轻和老年CBA/Ca小鼠的SL产生的IL-2量相当。在CBA/Ca小鼠的SL和腹股沟淋巴结(ILN)细胞之间也观察到对Con A的年龄相关反应差异。与SL相反,ILN细胞对Con A的增殖反应增强。然而,老年CBA/Ca小鼠经Con A刺激的ILN细胞产生的淋巴因子与老年CBA/Ca小鼠经Con A刺激的SL产生的淋巴因子相似。为了确定老年ILN T细胞对多克隆和抗原特异性刺激的反应是否相似,检测了从老年和年轻CBA/Ca小鼠的ILN分离的T细胞对钥孔戚血蓝蛋白(KLH)的反应。与用年轻KLH脉冲巨噬细胞(M phi)培养的年轻小鼠的KLH特异性T细胞相比,用老年小鼠的KLH脉冲M phi培养的老年小鼠的KLH特异性T细胞增殖能力显著降低。与预期结果相反,缺陷不在T细胞水平;用老年KLH脉冲M phi培养的年轻T细胞的增殖与用老年M phi培养的老年T细胞的增殖相当。这些结果表明,衰老对多克隆和抗原特异性T细胞增殖以及从不同淋巴器官和不同小鼠品系分离的T细胞的多克隆刺激有不同影响。