Negoro S, Hara H, Deguchi Y, Nishio S, Jia L, Wang J, Kishimoto S
Kekkaku. 1989 Oct;64(10):657-67.
It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
众所周知,与年龄相关的最显著免疫异常是针对外来抗原的免疫反应降低以及针对自身抗原的自身抗体产生增加。为了解释这些免疫异常,我们在细胞、分子和基因水平上研究了老年组和年轻组人淋巴细胞的各种功能。结果表明:第一,老年组的T细胞不仅对特异性抗原TAP,而且对有丝分裂原PHA或PMA与离子霉素的联合刺激,其增殖反应均显著降低。第二,在TAP和PHA刺激后,老年T细胞上IL-2受体的数量,尤其是高亲和力受体的数量显著减少。第三,老年T细胞表达IL-2R的Tac(p55)和p70/75以及内化与受体结合的重组IL-2的能力降低。第四,尽管老年B细胞对SAC刺激的增殖能力比年轻B细胞低两倍,但在用SAC和部分纯化的BCDF联合刺激后,基于回收的活细胞数量,其分化为IgG和IgA类ISC的能力反而增加。第五,老年T细胞产生的IL-2活性量比年轻T细胞少十倍,但在PHA刺激后,老年T细胞产生的BCDF活性量比年轻T细胞高两倍。当在同一样本中测定这两种活性时,发现IL-2活性与BCDF活性呈负相关。第六,PMA与离子霉素的联合刺激可诱导高度纯化的T细胞、T细胞亚群和B细胞产生增殖反应。CD-8阳性T细胞增殖反应的年龄相关下降程度最显著,CD-4阳性T细胞次之,B细胞最少。第七,尽管在刺激后2小时达到c-myc mRNA水平的最大值,且两个年龄组之间的量相似,但在8小时或24小时时,老年T细胞中的mRNA量比年轻T细胞中的量更高。c-myc mRNA降解率的降低似乎是原因。我们发现两个年龄组的T细胞中c-myb mRNA的最大量和动力学没有差异。(摘要截断于400字)