Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection

Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection
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DOI:
10.1086/590118
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发表时间:
2008-08-15
影响因子:
6.4
通讯作者:
Gerna, Giuseppe
Gerna, Giuseppe
中科院分区:
医学2区
文献类型:
--
作者:
Lilleri, Daniele;Fornara, Chiara;Gerna, Giuseppe

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背景。研究了人巨细胞病毒(HCMV)初次感染后特异性T细胞免疫的发展及其与病毒向胎儿传播的关系。在感染hcmv后的第一年,研究了21名免疫正常的孕妇(12名递质和9名非递质)和5名未怀孕的受试者中,hcmv特异性T细胞(受hcmv感染的树状细胞刺激)的膜表型(CCR7和CD45RA表达)和细胞内细胞因子(干扰素[IFN]- γ和白细胞介素-2)的产生。在第一个月很容易检测到产生ifn - γ的CD4(+)和CD8(+) T细胞,它们的水平随时间没有显著变化。在感染的早期和晚期,CCR7的表达都可以忽略不计。在CCR7(-)细胞中,重新表达CD45RA的细胞逐渐增加,直到hcmv特异性CD4(+)和CD8(+) T细胞分别达到33%(范围,7%-51%)和51%(范围,22%-76%)的中位水平,与远程感染受试者的观察结果相似。CD45RA再表达与HCMV从血液中消失相关。在感染后的第一个月内,hcmv特异性CD45RA(+) T细胞水平在传递性母亲中明显低于非传递性母亲。初次感染后,循环中的hcmv特异性效应T细胞恢复到CD45RA(+)表型,这似乎与病毒血症和垂直传播的控制有关。因此,这些细胞可能代表hcmv特异性池中长寿命的真记忆淋巴细胞。
Background. The development of human cytomegalovirus (HCMV)-specific T cell immunity after primary infection and its correlation with virus transmission to the fetus were investigated.Methods. The membrane phenotype (CCR7 and CD45RA expression) of and intracellular cytokine (interferon [IFN]-gamma and interleukin-2) production by HCMV-specific T cells (stimulated with HCMV-infected dendritic cells) were investigated in 21 immunocompetent pregnant women (12 transmitters and 9 nontransmitters) and in 5 nonpregnant subjects during the first year after infection.Results. IFN-gamma-producing CD4(+) and CD8(+) T cells were readily detected during the first month, and their levels did not significantly change with time. CCR7 expression was negligible during both the early and the late stage of infection. Among CCR7(-) cells, those reexpressing CD45RA progressively increased until they reached median levels of 33% (range, 7%-51%) and 51% (range, 22%-76%) for HCMV-specific CD4(+) and CD8(+) T cells, respectively, similar to those observed in subjects with remote infection. CD45RA reexpression correlated with HCMV disappearance from blood. The level of HCMV-specific CD45RA(+) T cells during the first months after infection was significantly lower in mothers who were transmitters than in those who were nontransmitters.Conclusions. After primary infection, circulating HCMV-specific effector T cells revert to the CD45RA(+) phenotype, which appears to be associated with control of viremia and vertical transmission. Thus, these cells may represent long-lived true memory lymphocytes in the HCMV-specific pool.