Streeck Hendrik, van Bockel David, Kelleher Anthony
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin HIV AIDS. 2008 Jan;3(1):52-9. doi: 10.1097/COH.0b013e3282f269d6.
Important immunological events, especially involving T cells, occur during primary HIV-1 infection. The qualitative nature of the primary immune response to the virus may determine long-term outcome. Whereas CD4 T cells are being rapidly depleted, CD8 T cells play an important role in the initial control of viral replication. There is significant individual variability in the extent of viral control. Understanding the mechanisms underlying these differences and the causes of the development of dysfunctional T-cell responses will allow the identification of opportunities for therapeutic intervention that might change the long-term outcome.
Recent studies have revealed early dysfunction of T cells demonstrating increased expression of PD-1, CTLA-4 and reduced expression of CD127. Those studies suggest disruption of the interaction between CD4 and CD8 T cells. In addition, a few regions, mainly within the Gag protein, have been highlighted as potentially important targets for effective immune responses inducing viral control.
Despite recent studies emphasizing the critical nature of acute HIV-1 infection, current intervention strategies have failed to influence disease progression. Recent findings have indicated potential new strategies to re-enable functional properties of T cells and direct these responses towards critical regions of the virus.
重要的免疫事件，尤其是涉及T细胞的免疫事件，发生在原发性HIV-1感染期间。对该病毒的原发性免疫反应的性质可能决定长期结果。在CD4 T细胞迅速耗竭的同时，CD8 T细胞在病毒复制的初始控制中发挥重要作用。病毒控制的程度存在显著的个体差异。了解这些差异背后的机制以及功能失调的T细胞反应发展的原因，将有助于确定可能改变长期结果的治疗干预机会。
最近的研究揭示了T细胞的早期功能障碍，表现为PD-1、CTLA-4表达增加以及CD127表达降低。这些研究表明CD4和CD8 T细胞之间的相互作用受到破坏。此外，一些区域，主要是在Gag蛋白内，已被强调为诱导病毒控制的有效免疫反应的潜在重要靶点。
尽管最近的研究强调了急性HIV-1感染的关键性质，但目前的干预策略未能影响疾病进展。最近的发现表明了潜在的新策略，可重新激活T细胞的功能特性，并将这些反应导向病毒的关键区域。
