The presence of persistent, latent HIV reservoirs in CD4⁺ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8⁺ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4⁺ T cells. Here, we have shown that treating CD4⁺ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8⁺ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8⁺ T cells recognized and potently eliminated CD4⁺ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8⁺ T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to CD8⁺ T cells that may need to be addressed to cure infection.

中文翻译：

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潜在的HIV储库表现出固有的抗CD8 ⁺ T细胞清除能力

CD4 ⁺ T细胞中存在持久性潜伏的HIV储集层，阻碍了目前为治愈感染所做的努力。所谓的踢杀模式建议通过将潜伏时间逆转剂与免疫效应物（例如细胞毒性T淋巴细胞）结合使用来清除这些储库。对这种方法的支持主要取决于潜伏期模型的成功，这些模型不能完全反映长期抗逆转录病毒疗法（ART）的个体潜伏性水库的组成。最近的研究表明，CD8 ⁺ T细胞具有识别缺陷前病毒的潜力，前病毒占所有受感染细胞的绝大部分，并且由于受感染CD4 ^+的体内克隆扩增，随着时间的流逝，前病毒的格局可以形成。T细胞。在这里，我们已经表明，治疗的CD4 ⁺从ART治疗的个体的T细胞具有强效延迟逆转剂和自体CD8的组合⁺持续减少细胞结合的HIV DNA的T细胞，但未能耗尽复制能力的病毒。这些CD8 ⁺ T细胞识别并有效消除了新近感染自体贮库病毒的CD4 ⁺ T细胞，排除了免疫逃逸和CD8 ⁺ T细胞功能障碍的作用。因此，我们的结果表明，具有复制能力的HIV的细胞具有对CD8 ⁺ T细胞的固有抗性，这可能需要解决以治愈感染。