Poor HIV control in HLA-B*27 and B*57/58 noncontrollers is associated with limited number of polyfunctional Gag p24-specific CD8+ T cells

Poor HIV control in HLA-B*27 and B*57/58 noncontrollers is associated with limited number of polyfunctional Gag p24-specific CD8+ T cells
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HLA-B*27 和 B*57/58 非控制者中 HIV 控制不佳与多功能 Gag p24 特异性 CD8 T 细胞数量有限有关

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发表时间:
2013
期刊:
AIDS (London)
影响因子:
--
通讯作者:
P. Hansasuta
P. Hansasuta
中科院分区:
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文献类型:
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作者:
N. Techakriengkrai;Y. Tansiri;P. Hansasuta

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目的:分析HIV控制者的免疫应答,为我们研究宿主免疫应答在HIV控制中的作用提供了一个机会。设计:在本研究中,在两组临床上不同的HLA-B*27、HLA-B*57/58匹配个体、病毒血症控制者[血浆HIV载量(pVL)≤ 2000拷贝/ml]和非控制者(pVL >2000拷贝/ml)中评估HIV Gag p24特异性CD 8 + T细胞应答的功能质量,以确定其对自然HIV临床结果的影响。  方法:使用体外干扰素(IFN)-ELISpot试验筛选每个个体的HIV Gag p24特异性T细胞应答。细胞内细胞因子染色测定用于确定它们的功能质量(作为产生的细胞因子的数量)。结果:我们发现,与以往的研究相比,所有泰国志愿者与HLA-B*5801是统一的noncontrollers。病毒血症控制者的高功能性p24特异性CD 8 + T细胞数量显著多于非病毒血症控制者(P <0.05)。  在总p24和表位特异性水平上均观察到这种上级应答质量。此外,高功能质量Gag p24特异性CD 8 + T细胞的绝对数量与pVL显著负相关(r =-0.6984,P = 0.0006),并且与CD 4 + T细胞计数显著正相关(r = 0.5648,P = 0.0095)。        结论:我们得出结论,足够数量的高功能质量Gag p24特异性CD 8 + T细胞与天然HIV控制者状态密切相关。
Objectives:Analysis of immune response in HIV controllers, a unique group of infected individuals who are able to control HIV naturally, has provided us a chance to investigate the roles of host immune responses in HIV control. Design:In this study, the functional quality of HIV Gag p24-specific CD8+ T-cell responses was assessed in two groups of clinically distinct, HLA-B*27, HLA-B*57/58-matched individuals, viremic controllers [plasma HIV load (pVL) ⩽2000 copies/ml) and noncontrollers (pVL >2000 copies/ml) to determine its impacts on natural HIV clinical outcome. Methods:An ex-vivo interferon (IFN)-&ggr; ELISpot assay was used to screen for each individual's HIV Gag p24-specific T-cell responses. Intracellular cytokine staining assay was used to determine their functional quality (as number of cytokine being produced). Results:We found that, in contrast to previous studies, all Thai volunteers with HLA-B*5801 were uniformly noncontrollers. Viremic controllers were observed with a significantly larger number of high functional quality p24-specific CD8+ T cells than noncontrollers (P < 0.05). This superior quality of responses was observed at both total p24 and epitope-specific level. Moreover, the absolute number of high functional quality Gag p24-specific CD8+ T cells was significantly in a negative correlation with pVL (r = −0.6984, P = 0.0006) and also in a positive correlation with CD4+ T-cell count (r = 0.5648, P = 0.0095). Conclusion:We concluded that an adequate number of high functional quality Gag p24-specific CD8+ T cells is strongly associated with a natural HIV controller status.
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发表时间: 2006-06-15
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