Jambo Kondwani C, Sepako Enoch, Glennie Sarah J, Mzinza David, Williams Neil A, Gordon Stephen B, Heyderman Robert S
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
PLoS One. 2012;7(6):e38628. doi: 10.1371/journal.pone.0038628. Epub 2012 Jun 8.
Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART.
Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity.
We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood.
Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations.
季节性流感与艾滋病患者更高的发病率和死亡率相关。高效抗逆转录病毒治疗（HAART）已使流感相关并发症有所减少，但在非洲环境中自然获得的针对流感病毒的T细胞免疫的性质，以及HAART后免疫重建如何改变这种免疫尚不清楚。我们测量了未免疫的感染HIV的马拉维成年人中流感特异性CD4(+) T细胞免疫，然后研究了HAART后的免疫重建情况。
从感染HIV和未感染HIV的马拉维成年人中分离外周血单个核细胞。基于CFSE增殖和CD154表达的流式细胞术检测用于测量流感特异性CD4(+) T细胞免疫。
我们发现艾滋病患者中自然获得的增殖性流感特异性CD4(+) T细胞反应较低，在CD4计数相对较高（>350个细胞/微升）的无症状感染HIV的成年人中也存在这种情况。接受HAART治疗12个月的HIV感染患者中，尽管病毒载量显著降低且CD4计数增加，但流感特异性CD4(+) T细胞免疫重建情况较差。这种不良的免疫重建表现为外周血中流感特异性增殖性CD4(+) T细胞反应较低以及表达CD154的流感特异性CD4(+) T细胞比例降低。
我们的数据表明，无症状感染HIV的成年人也可能有患流感相关并发症的风险，并且仅HAART可能无法规避艾滋病患者的这种风险。本研究强调需要在HIV感染早期确定可能的干预措施以降低流感风险，并加强对这些易感非洲人群的流感监测。
