MEMORY LYMPHOCYTE-T HYPORESPONSIVENESS TO NON-COGNATE STIMULI - A KEY FACTOR IN AGE-RELATED IMMUNODEFICIENCY
MEMORY LYMPHOCYTE-T HYPORESPONSIVENESS TO NON-COGNATE STIMULI - A KEY FACTOR IN AGE-RELATED IMMUNODEFICIENCY
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DOI：
10.1002/eji.1830220408
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发表时间：
1992-04-01
影响因子：
5.4
通讯作者：
MILLER, RA
中科院分区：
文献类型：
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作者：
FLURKEY, K;STADECKER, M;MILLER, RA
我们实验室先前的研究表明，衰老会导致表达高水平CD44的细胞积累，CD44被认为是记忆淋巴细胞的标志物。并且，从任何年龄的小鼠中正向筛选出的CD44hi T细胞，在白细胞介素（IL）-2产生细胞的有限稀释评估中，对刀豆蛋白A（Con A）的反应较差。我们现在报告对老年和年轻小鼠的记忆T细胞功能针对非同源激活剂（Con A和葡萄球菌肠毒素SEB）进行更全面分析的结果。我们报告，通过去除带有CD45RB决定簇的细胞而分离出的记忆T细胞，在有限稀释培养条件下，无论是通过IL - 2还是IL - 3的积累来衡量反应，能够对Con A或SEB作出反应的细胞都非常少。作为对照，我们表明记忆T细胞在有限稀释时确实对近期接触过的致敏抗原，即曼氏血吸虫卵抗原，有强烈反应；因此，当同源刺激作用于抗原特异性细胞时，有限稀释培养方案并不排除记忆T细胞的激活。这些数据表明，初始T细胞和记忆T细胞在激活要求上可能存在根本差异，并进一步表明，随着年龄的增长记忆T细胞的积累是老年小鼠对非同源有丝分裂原反应性低的原因。
Previous studies from our laboratory have suggested that aging leads to an accumulation of cells expressing high levels of CD44, thought to be a marker for memory lymphocytes. and that positively selected CD44hi T cells, from mice of any age, respond poorly to concanavalin A (Con A) in limiting dilution estimates of interleukin (IL)-2-producing cells. We now report the results of a more comprehensive analysis of memory T cell function, in old and young mice, to non-cognate activators (Con A and the staphylococcal enterotoxin SEB). We report that memory T cells. isolated by removing cells bearing the CD45RB determinant, contain very few cells able to respond to either Con A or SEB under limiting dilution culture conditions. whether the responses are measured by IL-2 or by IL-3 accumulation. As a control, we show that memory T cells do respond strongly at limiting dilution, to recently encountered priming antigens, i.e. Schistosoma mansoni egg antigen; the limiting dilution culture protocol thus does not preclude activation of memory T cells when cognate stimuli are presented to antigen-specific cells. These data suggest that virgin and memory T cells may differ fundamentally in their activation requirements, and suggest further that the accumulation, with age, of memory T cells accounts for the low responsiveness of old mice to non-cognate mitogens.