REGULATION OF LYMPHOCYTE PROLIFERATION AND CELL CYCLE PROGRESSION

人类幼稚的复制历史和复制潜力 记忆T细胞是淋巴细胞生物学的关键参数 分析过了。端粒是一种独特的末端染色体结构， 在体外随着细胞分裂而缩短，在体内随年龄增加而缩短 人类体细胞。我们评估了端粒长度作为一种测量端粒长度的方法 活体复制幼稚和记忆性人类T细胞的历史，并发现 端粒末端限制性片段长1.40.1kb。 来自相同捐赠者的记忆细胞中的CD4+幼稚T细胞， 这种关系在广泛的捐赠者年龄范围内是恒定的。这 表明记忆细胞从幼稚的前体细胞分化而来 发生大量的克隆扩张，这种扩张在很长一段时间内都是相似的 射程。幼稚细胞的体外复制能力是128倍 比来自相同捐赠者的记忆细胞的数量要大。人类CD4+幼稚 因此，正如所反映的那样，记忆细胞在体内的复制历史上不同 端粒长度以及它们的剩余复制能力。 这些关系可能对艾滋病毒等病理疾病具有重要意义 感染，在这种感染中，CD4+T细胞的产生可能受到影响， 体内扩增的细胞介导的治疗干预 对于治疗效果来说是必不可少的。 端粒酶，一种核糖核蛋白，能够合成 端粒重复序列，在生殖系和恶性细胞中表达，是 在大多数正常人的体细胞中不存在。基因的选择性表达 因此，端粒酶被认为是长生不老的基础 生殖系和恶性细胞。当对端粒酶活性进行分析时 研究发现，端粒酶在人T淋巴细胞中表达。 胸腺细胞中的高水平，扁桃体T细胞中的中等水平， 外周血液中T细胞的水平很低，甚至检测不到。此外， 端粒酶活性在外周T淋巴细胞中被高度诱导 通过CD3和CD28激活(抗CD3/CD28)。端粒酶可能因此发挥作用 在T细胞发育和决定T细胞能力中的允许作用 用于克隆扩增的淋巴样细胞。

The replicative history and replicative potential of human naive and memory T cells, critical parameters of lymphocyte biology, were analyzed. Telomeres are unique terminal chromosomal structures which shorten with cell division in vitro and with increased age in vivo for human somatic cells. We assessed telomere length as a measure of the in vivo replicative history of naive and memory human T cells, and found that telomeric terminal restriction fragments were 1.4 0.1 kb longer in CD4+ naive T cells than in memory cells from the same donors, a relationship that was constant over a wide range of donor age. This suggests that the differentiation of memory cells from naive precursors occurs with substantial clonal expansion that is similar over a wide age range. The in vitro replicative capacity of naive cells was 128-fold greater than that of memory cells from the same donors. Human CD4+ naive and memory cells thus differ in in vivo replicative history as reflected in telomeric length as well as in their residual replicative capacity. These relationships may be significant for pathologies such as HIV infection, in which CD4+ T cell generation may be compromised, and for therapeutic interventions mediated by cells whose in vivo expansion is essential for therapeutic effect. Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. When telomerase activity was analyzed in normal human T lymphocytes, it was found that telomerase is expressed at a high level in thymocytes, at an intermediate level in tonsil T cells, and at a low to undetectable level in peripheral blood T cells. Moreover, telomerase activity was highly inducible in peripheral T lymphocytes by activation through CD3 and CD28 (anti-CD3/CD28). Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for clonal expansion.