主页 > 医药科学 >
【medical-news】Bigger T-cell response not necessarily bett
T细胞反应更强不一定更好
Kirsty Minton
As the hunt for an effective vaccine against HIV continues, most researchers are focusing on inducing a virus-specific T-cell response to protect against disease progression. However, as high-frequency CD8+ T-cell responses can be detected in individuals who progress to AIDS, it is becoming increasingly important to define the most effective type of T-cell response. This study indicates that CD8+ T cells specific for multiple epitopes of the HIV capsid protein Gag are most effective at controlling chronic HIV infection, and challenges the assumption that a bigger T-cell response is always better regardless of specificity.
随着寻找有效的抗HIV疫苗的继续，大多数研究者都集中在研究诱导能够抵御疾病进展的病毒特异性T细胞反应。然而，艾滋病进展患者体内仍有较高水平的CD8阳性T细胞反应，这对如何定义最有效的T细胞反应类型有重要意义。这项研究提示，针对HIV衣壳蛋白gag多表位的特异性CD8阳性T细胞是控制慢性HIV感染最有效的，这对过去认为的无论特异性如何，T细胞反应越强越好的理论提出了挑战。
The authors studied 578 HIV-infected adults from Durban, KwaZulu-Natal, South Africa, who had not had any form of antiretroviral therapy. For each individual, HLA typing and quantification of plasma viral load were carried out, and the CD8+ T-cell response to a panel of overlapping peptides covering the entire sequence of HIV-1 clade C was assessed.
作者研究了来自南非KwaZulu-Natal德班的578名HIV感染的成年人，这些人都未接受过任何抗逆转录病毒治疗。他们检测了每个对象的人类白细胞抗原分型和病毒载量，CD8阳性T细胞功能通过其与包含全部HIV-1进化枝C序列的重叠多肽反应来评估。
In general, T-cell responses specific for Gag epitopes were associated with lower levels of viraemia, whereas responses specific for epitopes of the viral envelope protein Env and of the accessory and regulatory proteins (Rev, Tat, Vif, Vpr, Vpu and Nef) were associated with higher viral loads. This association between the viral epitope targeted and viral load held true for individuals expressing the same HLA-B allele, which shows that the protein targeted is more important than the restricting HLA allele in determining viral load. Also, whereas an increase in the number of targeted Gag epitopes significantly decreased viral load, an increase in the number of Env-specific responses led to an increase in viral load.
一般的，针对gag表位的特异性T细胞反应与低水平的病毒血症相关，而针对病毒包膜蛋白env、辅助和调节蛋白rev、tat、vif、vpr、vpu、nef表位的特异性T细胞反应与高病毒载量相关。而且，gag表位靶向的数目增加，病毒载量明显下降，而env特异性的反应数目增加，病毒载量则升高。
Therefore, not all CD8+ T-cell responses are associated with effective control of HIV, and in some cases increasing the breadth of the response could worsen control of the disease. When the entire study population was analysed, it was shown that individuals with T-cell responses to both Gag epitopes and epitopes of Env and/or of the accessory and regulatory HIV proteins had higher viral loads than individuals with responses to Gag epitopes only. This indicates that responses to Env and the accessory and regulatory protein epitopes might have a negative effect on the Gag-specific response.
因此，并不是所有的T细胞反应都与有效控制HIV相关，一些时候，反应过宽将导致疾病控制恶化。当分析整个研究人群时，结果表明，拥有gag、env和/或辅助蛋白和调节蛋白表位T细胞反应的患者，病毒载量较高，而单纯拥有gag表位T细胞反应的患者，病毒载量较低。
This large population-based study, which shows that broad Gag-specific responses are most effective in the control of chronic HIV infection, lends support to previous smaller studies that indicate the potential importance of Gag as an immunogen. However, this does not rule out the possibility that non-Gag-specific responses could successfully control viraemia when vaccinated individuals become infected with HIV. It remains to be determined whether Env-specific CD8+ T-cell responses are less effective than Gag-specific responses, or whether Env-specific responses are equally effective but are only recruited later in natural infection, as Env (unlike Gag) depends on de novo synthesis before processing and presentation on the surface of infected cells for recognition by CD8+ T cells.
这项大规模人群的研究表明，宽广的gag特异性反应是控制明显HIV感染最有效的，同时支持过去的一些小规模研究结论，提示gag作为免疫原的潜在重要性。然而，该研究不能排除当接受疫苗的个体感染HIV后，其他非gag特异性反应能够成功控制病毒血症的可能性。仍然不能确定，是否CD8阳性特异性T细胞反应不如gag特异性反应有效，或者二者一样有效，只不过，en特异性反应发生在自然感染之后，因为env在感染细胞表面表达、合成并被CD8阳性T细胞识别前，依靠从头合成。 好，很有帮助，谢谢
阅读本文的人还阅读：
作者:admin@医学,生命科学 2010-12-07 17:11
医学,生命科学网