Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts.

Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts.
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DOI:
10.4049/jimmunol.156.10.3587
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发表时间:
1996-05
影响因子:
4.4
通讯作者:
J. Monteiro;F. Batliwalla;Harry Ostrer;Peter K. Gregersen
J. Monteiro;F. Batliwalla;Harry Ostrer;Peter K. Gregersen
中科院分区:
医学2区
文献类型:
--
作者:
J. Monteiro;F. Batliwalla;Harry Ostrer;Peter K. Gregersen

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克隆扩增的CD 8 +T细胞(通常在CD 57+或CD 28-亚群中发现)的长期体外培养通常不成功,表明这些细胞可能具有有限的复制潜力。端粒缩短可能反映了“有丝分裂钟”的作用,它调节细胞可以经历的分裂次数。在这项研究中,我们比较了10个正常人的CD 28-CD 8+和CD 28 + CD 8 + T细胞的端粒长度,以评估其复制历史。总体而言,发现与CD 28 + CD 8+亚群相比,CD 28-CD 8 + T细胞亚群中的端粒长度显著较短。此外,来自个体的克隆扩增的TCRBV 11 + CD 8 + T细胞显示端粒长度比多克隆CD 28 + CD 8 + T细胞亚群中发现的端粒长度短2.9kb。这些发现表明,克隆扩增的CD 28-CD 8 + T细胞比CD 28 + CD 8 + T细胞经历了更多轮的复制,并且与CD 28表达的丧失一致,它们可能已经达到复制性衰老的状态。
Long term in vitro culture of clonally expanded CD8+T cells, generally found within the CD57+ or CD28-subset, has generally been unsuccessful, suggesting that these cells may have a limited replicative potential. Telomeric shortening may reflect the action of a "mitotic clock" regulating the number of divisions a cell can undergo. In this study, we have compared the telomeric lengths of CD28-CD8+ and CD28+CD8+ T cells in 10 normal individuals to assess their replicative history. Overall, the telomeric lengths were found to be significantly shorter in the CD28-CD8+ T cell subset compared with the CD28+CD8+ subset. Furthermore, clonally expanded TCRBV11+CD8+ T cells from an individual exhibited telomeric lengths that were 2.9 kb shorter than those found in the polyclonal CD28+CD8+ T cell subset. These findings indicate that clonally expanded CD28-CD8+ T cells have undergone many more rounds of replication than CD28+CD8+ T cells, and consistent with the loss of CD28 expression, they may have reached a state of replicative senescence.