CELLULAR DETERMINANTS OF AGE-RELATED DECREMENTS IN THE T-CELL MITOGEN RESPONSE OF B6CBAF1 MICE

CELLULAR DETERMINANTS OF AGE-RELATED DECREMENTS IN THE T-CELL MITOGEN RESPONSE OF B6CBAF1 MICE
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DOI:
10.1093/geronj/47.4.b115
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发表时间:
1992-07-01
期刊:
JOURNALS OF GERONTOLOGY
影响因子:
--
通讯作者:
HARRISON, DE
HARRISON, DE
中科院分区:
其他
文献类型:
--
作者:
FLURKEY, K;MILLER, RA;HARRISON, DE

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在B6 CBAF 1小鼠中发现了与T细胞有丝分裂原的增殖反应受损相关的免疫系统细胞组成的变化。ConA诱导的IL-2分泌细胞(pHTL)和ConA诱导的细胞毒性细胞(pCTL),通过有限稀释分析确定的前体的频率较低的脾细胞从老年小鼠,作为ConA和PHA的增殖反应,确定在传统的高细胞密度培养相同的小鼠。pHTL频率与ConA(r2 = 0.94)和PHA(r2 = 0.83)的增殖反应在老年小鼠中,但不年轻;有没有相关性pCTL频率与增殖反应。老年小鼠中pHTL频率降低的原因是:(a)稀释T细胞的脾B细胞数量出现与年龄相关的倍增,以及(B)尽管脾CD 4+和CD 8+细胞总数保持正常,但脾中Con A反应性pHTL细胞的绝对数量出现67%的下降。因此,绝对pHTL数量下降和脾脏中非T细胞数量增加均导致pHTL频率降低,这与老年B6 CBAF 1小鼠中观察到的有丝分裂原应答受损密切相关。
Age-related changes in the cellular composition of the immune system that are associated with an impaired proliferative response to T-cell mitogens were identified for B6CBAF1 mice. The frequencies of precursors of Con A-induced IL-2-secreting cells (pHTL) and of Con A-induced cytotoxic cells (pCTL), determined by limiting dilution analysis, were lower for splenocytes from old mice, as were the proliferative responses to Con A and PHA, determined in conventional high cell density cultures for the same mice. The pHTL frequency correlated with the proliferative response to Con A (r2 = .94) and to PHA (r2 = .83) among old mice, but not among young; there were no correlations of pCTL frequency with proliferative responses. The reduced pHTL frequency in old mice resulted from: (a) an age-related doubling of the number of splenic B cells that diluted T cells, and (b) a 67% decline in the absolute number of Con A-reactive pHTL cells in the spleen that appeared despite the maintenance of normal numbers of total splenic CD4+ and CD8+ cells. Thus, both a decline in absolute pHTL numbers and an increase in the number of non-T cells in the spleen result in a diminished pHTL frequency that is closely linked to the impaired mitogen response observed for old B6CBAF1 mice.