Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection

被引:125
作者
Brunetta, Enrico [1 ,2 ]
Fogli, Manuela [2 ]
Varchetta, Stefania [3 ,4 ]
Bozzo, Luisa [1 ]
Hudspeth, Kelly L. [5 ]
Marcenaro, Emanuela [6 ]
Moretta, Alessandro [6 ]
Mavilio, Domenico [1 ]
机构
[1] Ist Clin Humanitas, Clin & Expt Immunol Lab, IRCCS, Milan, Italy
[2] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
[3] Policlin San Matteo, Ctr Hepatol & Infect Dis, Pavia, Italy
[4] Univ Pavia, I-27100 Pavia, Italy
[5] Rush Univ, Dept Immunol & Microbiol, Med Ctr, Chicago, IL 60612 USA
[6] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy
关键词
antiretroviral therapy; biomarker; human cytomegalovirus coinfection; natural killer cell subsets; NKG2A/NKG2C ratio; NK CELLS; RECEPTOR EXPRESSION; INFECTION;
D O I
10.1097/QAD.0b013e3283328d1f
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: The HIV-1-induced expansion of highly dysfunctional natural killer (NK) cell subsets represents a strategy to evade NK cell antiviral functions. In this context, the loss of NKG2A(pos) NK cells in chronic viremic HIV-1-infected individuals has also been associated with a dramatic expansion of NKG2C(pos) NK cells. The viral trigger associated with high frequencies of NK cell subsets expressing NKG2C is still being debated. Objective: To confirm that human cytomegalovirus (HCMV) infection is necessary for the expansion of NKG2C(pos) NK cells and to assess whether this phenomenon affects NKG2A/NKG2C ratio on NK cells in patients coinfected with HIV-1 and HCMV. Design: We measured the expression of NKG2A and NKG2C on NK cells from 70 healthy donors, 21 early, 96 chronic and 27 long-term nonprogressor's (LTNPs) HIV-1 infected patients using a multicolor flow cytometric approach. HCMV infection was detected by titrating the serum levels of specific circulating antibodies. Results: A significant expansion of NKG2C(pos) NK cells could be detected only in HCMV-infected patients. This phenotypic feature, together with the HIV-1-mediated downmodulation of NKG2A, pathologically reverses the ratio of NKG2A/NKG2C uniquely on NK cells from chronic viremic HIV-1-infected patients with a concomitant HCMV infection. The normalization of NKG2A/NKG2C ratio to values more than one occurred only after 24 Months Of Suppression of HIV-1 replication following antiretroviral therapy. Conclusion: The inversion of NKG2A/NKG2C ratio characterizes advanced stages of HIV-1 disease in patients showing a concomitant HCMV infection. This NK cell immune parameter renders this cohort of patients distinguishable from LTNPs and early HIV-1-infected individuals. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
引用
收藏
页码:27 / 34
页数:8
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