Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+ CD45RA+ CD27- T cells: the potential involvement of interleukin-7 in this process
Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+ CD45RA+ CD27- T cells: the potential involvement of interleukin-7 in this process
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DOI：
10.1111/j.1365-2567.2010.03386.x
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发表时间：
2011-03-01
期刊：
影响因子：
6.4
通讯作者：
Akbar, Arne N.
中科院分区：
文献类型：
--
作者：
Libri, Valentina;Azevedo, Rita I.;Akbar, Arne N.
衰老和终生巨细胞病毒（CMV）感染在塑造健康老年人初始和记忆CD4+ t细胞库中的相对作用尚不清楚。通过多元线性回归分析，我们发现年龄本身比CMV血清阳性更能预测CD45RA+ CD27+ CD4+ T细胞随时间的减少。相比之下，CD45RA- CD27-和CD45RA+ CD27- CD4+ T细胞的增加几乎完全是CMV血清阳性的结果，年龄本身没有显著影响。此外，在cmv血清阳性供者中，大多数CD45RA- CD27-和CD45RA+ CD27- CD4+ T细胞对这种病毒具有特异性。与同一供体的其他T细胞亚群相比，CD45RA+ CD27- CD4+ T细胞显著降低CD28、白细胞介素-7受体α (IL-7R α)和Bcl-2表达、Akt （ser473）磷酸化，并降低T细胞受体激活后的存活能力。尽管如此，CD45RA+ CD27-亚群与CD45RA- CD27+和CD45RA- CD27- CD4+ t细胞亚群一样具有多功能，这表明它们不是一个耗尽的群体。此外，CD45RA+ CD27- CD4+ T细胞具有细胞毒性潜能，因为它们表达高水平的颗粒酶B和穿孔素。CD45RA- CD27+群体通过添加IL-7可产生重新表达CD45RA的CD4+记忆T细胞，在此过程中，这些细胞下调IL-7R和Bcl-2的表达，因此与体内同类细胞相似。最后，我们发现骨髓中多种特异性的CD45RA+ CD27- CD4+ T细胞的比例明显高于同一个体的血液，这表明骨髓可能是这些细胞产生的地方。
P>The relative roles that ageing and lifelong cytomegalovirus (CMV) infection have in shaping naive and memory CD4+ T-cell repertoires in healthy older people is unclear. Using multiple linear regression analysis we found that age itself is a stronger predictor than CMV seropositivity for the decrease in CD45RA+ CD27+ CD4+ T cells over time. In contrast, the increase in CD45RA- CD27- and CD45RA+ CD27- CD4+ T cells is almost exclusively the result of CMV seropositivity, with age alone having no significant effect. Furthermore, the majority of the CD45RA- CD27- and CD45RA+ CD27- CD4+ T cells in CMV-seropositive donors are specific for this virus. CD45RA+ CD27- CD4+ T cells have significantly reduced CD28, interleukin-7 receptor alpha (IL-7R alpha) and Bcl-2 expression, Akt (ser473) phosphorylation and reduced ability to survive after T-cell receptor activation compared with the other T-cell subsets in the same donors. Despite this, the CD45RA+ CD27- subset is as multifunctional as the CD45RA- CD27+ and CD45RA- CD27- CD4+ T-cell subsets, indicating that they are not an exhausted population. In addition, CD45RA+ CD27- CD4+ T cells have cytotoxic potential as they express high levels of granzyme B and perforin. CD4+ memory T cells re-expressing CD45RA can be generated from the CD45RA- CD27+ population by the addition of IL-7 and during this process these cells down-regulated expression of IL-7R and Bcl-2 and so resemble their counterparts in vivo. Finally we showed that the proportion of CD45RA+ CD27- CD4+ T cells of multiple specificities was significantly higher in the bone marrow than the blood of the same individuals, suggesting that this may be a site where these cells are generated.