Zharhary D, Segev Y, Gershon H E
Mech Ageing Dev. 1984 Apr-May;25(1-2):129-40. doi: 10.1016/0047-6374(84)90135-0.
Specific T-cell cytotoxic responses to allogeneic and hapten-modified syngeneic cells decrease with age. In order to determine the causes of these reduced T-cell cytotoxic responses, spleen cells from individual young and senescent C57BL/6J female mice were mixed in various proportions in culture with either X-irradiated BALB/c spleen cells or trinitrophenyl-modified syngeneic cells and the resultant cytotoxic responses determined in comparison to those of spleen cells from young and old mice stimulated alone. In both allogeneic and hapten-modified syngeneic cytotoxicity, it was found that a low percentage of the aged mice suffered from decreased helper-cell activity or from increase of suppressor activity, while the majority of mice showed no synergy, positive or negative, with the cells from the young donor. Studies of interleukin-2 (IL-2) activity were performed on conditioned medium from spleen cells from mice of various ages cultured for 24 h with concanavalin A. Those preparations from senescent mice that showed reduced IL-2 activity did not contain activity suppressive or competitive to IL-2 produced by spleen cells from young mice. Limiting dilution of spleen cells from mice of various ages in the presence of semi-allogeneic stimulatory cells and subsequent assay of the resultant allogeneic cytotoxicity provided a measure of the frequency of cytotoxic units. Parallel experiments in which crude IL-2 was added to the limit dilution cultures provided a measure of the frequency of cytotoxic cell precursors. Once again in these experiments, individual senescent mice demonstrated different defects. Three different types of age-related defects were observed. Certain aged mice were devoid of detectable cytotoxic units and cytotoxic T-lymphocyte precursor at the cell dilutions used. Other senescent mice demonstrated a very low frequency of cytotoxic units (approximately 1/40 000) as compared with young mice (approximately 1/5 000), and the addition of crude IL-2 to cultures from these mice did not improve reactivity. A third group of old mice, those with a moderate age-related decrease in the frequency of cytotoxic units (approximately 1/12 000), demonstrated a cytotoxic T-lymphocyte precursor frequency in the presence of crude IL-2 which was comparable to that of young mice (approximately 1/1000).
对异基因细胞和经半抗原修饰的同基因细胞的特异性T细胞细胞毒性反应会随着年龄的增长而降低。为了确定这些T细胞细胞毒性反应降低的原因，将来自年轻和衰老的C57BL/6J雌性小鼠个体的脾细胞以不同比例与经X射线照射的BALB/c脾细胞或三硝基苯基修饰的同基因细胞在培养中混合，并将由此产生的细胞毒性反应与单独刺激的年轻和年老小鼠的脾细胞的细胞毒性反应进行比较。在异基因和经半抗原修饰的同基因细胞毒性实验中，发现低比例的老年小鼠存在辅助细胞活性降低或抑制活性增加的情况，而大多数小鼠与年轻供体的细胞没有协同作用，无论是正向还是负向。对用伴刀豆球蛋白A培养24小时的不同年龄小鼠的脾细胞条件培养基进行了白细胞介素-2（IL-2）活性研究。那些来自衰老小鼠且显示IL-2活性降低的制剂中不含有对年轻小鼠脾细胞产生的IL-2有抑制或竞争作用的活性物质。在半异基因刺激细胞存在的情况下对不同年龄小鼠的脾细胞进行有限稀释，随后测定由此产生的异基因细胞毒性，提供了细胞毒性单位频率的一种度量。在有限稀释培养物中添加粗制IL-2的平行实验提供了细胞毒性细胞前体频率的一种度量。在这些实验中，老年小鼠个体再次表现出不同的缺陷。观察到三种不同类型的与年龄相关的缺陷。某些老年小鼠在所使用的细胞稀释度下没有可检测到的细胞毒性单位和细胞毒性T淋巴细胞前体。与年轻小鼠（约1/5000）相比，其他衰老小鼠表现出非常低的细胞毒性单位频率（约1/40000），并且向这些小鼠的培养物中添加粗制IL-2并没有提高反应性。第三组老年小鼠，即细胞毒性单位频率有中度年龄相关下降（约1/12000）的小鼠，在存在粗制IL-2的情况下表现出与年轻小鼠相当的细胞毒性T淋巴细胞前体频率（约1/1000）。
