Antigen-independent changes in naive CD4 T cells with aging.
Antigen-independent changes in naive CD4 T cells with aging.
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DOI：
10.1084/jem.184.5.1891
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发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Swain SL
中科院分区：
文献类型：
--
作者：
Linton PJ;Haynes L;Klinman NR;Swain SL
在老年人中，CD4 + T细胞群内发生显著变化，具有记忆表型且反应性明显降低的细胞比例增加。为了确定衰老表型的哪些方面取决于与环境中抗原的反复接触，我们检测了从TCR转基因小鼠中分离出的CD4 +细胞。有充分证据表明，在动物所处环境中未发现针对识别鸽细胞色素c的转基因TCR的交叉反应性抗原，因此转基因CD4 +细胞随年龄增长发生的改变很可能是由不依赖抗原的过程导致的。我们发现，在老年动物中，TCR转基因阳性的CD4 +细胞尽管数量和抗原反应性降低，但仍保持初始表型，而非呈现典型的衰老记忆表型。相反，转基因阴性的CD4 +细胞比例增加且表达衰老表型。与它们的初始状态一致，老年个体的转基因阳性细胞仍为CD44低表达、CD45RB高表达，在抗原刺激下分泌白细胞介素 - 2（IL - 2）而非白细胞介素 - 4（IL - 4）或干扰素 - γ（IFN - γ），并且需要共刺激才能对抗CD3刺激产生增殖反应。这些发现表明，向表达记忆表型的CD4细胞的衰老相关转变依赖于抗原刺激。然而，初始转基因阳性细胞抗原反应性的降低（表现为IL - 2和IL - 3分泌减少以及增殖能力降低）表明，随着衰老还会发生其他不依赖于抗原接触的内在变化。
In the elderly, a dramatic shift within the CD4+ T cell population occurs, with an increased proportion having a memory phenotype with markedly decreased responsiveness. To determine what aspects of the aged phenotype are dependent upon repeated contact with antigen in the environment, we examined CD4+ cells isolated from TCR Tg mice. There is good evidence that no cross-reacting antigens for the Tg TCR recognizing pigeon cytochrome c are found in the environment of the animal, so that alterations in the Tg CD4+ cells with aging are likely to be due to antigen-independent processes. We found that in aged animals, TCR transgene(pos) CD4+ cells, although decreased in number and antigen responsiveness, maintain a naive phenotype rather than acquiring a prototypical aged memory phenotype. In contrast, the population of transgene(1o-neg) CD4+ cells increase in proportion and express the aged phenotype. Consistent with their naive status, transgene(pos) cells of aged individuals remain CD44lo CD45RBhi, secrete IL-2 and not IL-4 or IFN-gamma upon antigenic stimulation, and require co-stimulation to proliferate to anti-CD3 stimulation. These findings suggest that the aging-associated shift to CD4 cells expressing the memory phenotype is dependent on antigenic stimulation. However, the decrease in antigen responsiveness of naive transgenepos cells, as revealed by a lower secretion of IL-2 and IL-3 and a lower proliferative capacity, suggests that additional intrinsic changes occur with aging that do not depend on encounter with antigen.
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影响因子：
5.4
作者：
BOMMHARDT, U;CEROTTINI, JC;MACDONALD, HR
通讯作者：
MACDONALD, HR
影响因子：
5.4
作者：
FLURKEY, K;STADECKER, M;MILLER, RA
通讯作者：
MILLER, RA
DOI：
10.1073/pnas.82.5.1508
发表时间：
1985-01-01
影响因子：
11.1
作者：
JEMMERSON, R;MORROW, PR;PATERSON, Y
通讯作者：
PATERSON, Y
影响因子：
5.4
作者：
KUBO, M;CINADER, B
通讯作者：
CINADER, B
影响因子：
4.3
作者：
EFFROS, RB;WALFORD, RL
通讯作者：
WALFORD, RL