Primary immune responses to human CMV: a critical role for IFN-γ-producing CD4+ T cells in protection against CMV disease

Primary immune responses to human CMV: a critical role for IFN-γ-producing CD4+ T cells in protection against CMV disease
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DOI:
10.1182/blood-2002-08-2502
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发表时间:
2003-04-01
期刊:
影响因子:
20.3
通讯作者:
Ten Berge, IJM
Ten Berge, IJM
中科院分区:
医学1区
文献类型:
--
作者:
Gamadia, LE;Remmerswaal, EBM;Ten Berge, IJM

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人类对致病病毒的保护性免疫的相关性仍有待阐明。我们确定了无症状和有症状肾移植受者原发性 CMV 感染过程中巨细胞病毒 (CMV) 特异性 CD4(+) 和 CD8(+) T 细胞的动力学和特征。无论临床症状如何,都会产生特异性 CD8(+) 细胞毒性 T 淋巴细胞 (CTL) 和抗体反应。 CD45RA(-)CD27(+)CCR7(-) CTL虽然在HIV感染中被归类为不成熟效应细胞,但在CMV保护性免疫反应的急性期是主要的CD8效应细胞群,并且具有功能能力。在无症状个体中,CMV 特异性 CD4(+) T 细胞反应先于 CMV 特异性 CD8(+) T 细胞反应,而在有症状个体中,CMV 特异性效应记忆 CD4(+) T 细胞反应延迟,只有在抗病毒治疗后才能检测到。这些患者出现的疾病症状表明功能性CD8+T细胞和抗体反应不足以控制病毒复制,而效应记忆CD4+T细胞的形成对于感染的恢复是必要的。
The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8(+) cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA(-)CD27(+)CCR7(-) CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4(+) T cells is necessary for recovery of infection.