Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
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DOI：
10.1182/blood-2002-07-2103
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Koup, RA
中科院分区：
文献类型：
--
作者：
Brenchley, JM;Karandikar, NJ;Koup, RA
病毒特异性CD 8（+）T细胞应答在限制病毒复制中起关键作用。这些反应的改变，如细胞溶解功能降低、不适当的成熟和有限的增殖能力，可能会降低其控制病毒复制的能力。在这里，我们报告了HIV特异性CD 8（+）T细胞分泌细胞因子和增殖反应HIM抗原刺激的能力。我们发现，在48小时的体外培养过程中，大部分产生细胞因子的HIV特异性CD 8（+）T细胞不能分裂和死亡。HIV特异性CD 8（+）T细胞增殖能力的缺乏是由CD 57的表面表达而不是由CD 28或CCR 7的缺乏所定义的。这种对抗原应答的增殖能力不能被外源性白细胞介素-2（IL-2）或IL-15克服。此外，CD 8（+）T细胞、CD 4（+）T细胞和INK细胞上的CD 57表达是增殖能力丧失、更多细胞分裂史和短端粒的一般标志。因此，我们认为，CD 57（+）HIV特异性CD 8（+）T细胞的增加是由慢性抗原刺激引起的，这是HIV感染的标志。因此，我们的研究确定了与HIV特异性CD 8（+）T细胞复制性衰老相关的表型，这可能对与慢性抗原刺激相关的其他疾病具有广泛的意义。
Virus-specific CD8(+) T-cell responses play a pivotal role in limiting viral replication. Alterations in these responses, such as decreased cytolytic function, inappropriate maturation, and limited proliferative ability could reduce their ability to control viral replication. Here, we report on the capacity of HIV-specific CD8(+) T cells to secrete cytokines and proliferate in response to HIM antigen stimulation. We find that a large proportion of HIV-specific CD8(+) T cells that produce cytokines in response to cognate antigen are unable to divide and die during a 48-hour in vitro culture. This lack of proliferative ability of HIV-specific CD8(+) T cells is defined by surface expression of CD57 but not by absence of CD28 or CCR7. This inability to proliferate in response to antigen cannot be overcome by exogenous interleukin-2 (IL-2) or IL-15. Furthermore, CD57 expression on CD8(+) T cells, CD4(+) T cells, and INK cells is a general marker of proliferative inability, a history of more cell divisions, and short telomeres. We suggest, therefore, that the increase in CD57(+) HIV-specific CD8(+) T cells results from chronic antigen stimulation that is a hallmark of HIV infection. Thus, our studies define a phenotype associated with replicative senescence in HIV-specific CD8(+) T cells, which may have broad implications to other conditions associated with chronic antigenic stimulation.