布里格姆总医院的拉根研究所David R. Collins课题组的最新研究揭示了CD8⁺ T细胞干细胞先于干预后的HIV病毒血症控制。相关论文于2025年12月1日发表于国际顶尖学术期刊《自然》杂志上。

在这里，课题组研究人员绘制和功能分析了CD8⁺ T细胞对来自bNAb受体ATI试验的纵向样本的自噬HIV表位的反应。PIC与卓越的干预前HIV特异性CD8+ T细胞增殖能力、干细胞样记忆表型和对自身同源的HIV肽脉冲CD4⁺ T细胞的回忆细胞毒性相关。给药bNAb后，CD8⁺ T细胞的干细胞性进一步增加，没有出现针对确定的HLA最佳表位的新克隆型。多模态单细胞分析揭示了与PIC和HIV特异性CD8⁺ T细胞干性相关的分子特征，包括代谢适应度和减少T细胞衰竭的特征。这些结果确定了在随后的PIC之前的免疫特征，为开发联合免疫疗法提供信息，这些联合免疫疗法将引起持久的HIV缓解。

据悉，为了避免终身抗逆转录病毒治疗（ART）的需要，需要干预措施来诱导持久的艾滋病毒缓解。在广泛中和性抗HIV-1抗体（bNAb）治疗和分析性治疗中断（ATI）后，在一部分个体中实现了病毒血症的持久干预后控制（PIC）。先前的研究支持CD8⁺ T细胞的作用，但CD8⁺ T细胞参与PIC的确切特征尚不清楚。

附：英文原文

Title: CD8+ T cell stemness precedes post-intervention control of HIV viremia

Author: Kiani, Zahra, Urbach, Jonathan M., Wisner, Hannah, Olatotse, Mpho J., Chang, Daniel Y., Acklin, Joshua A., Piechocka-Trocha, Alicja, Bonheur, Nathalie, Khatri, Ashok, Lichterfeld, Mathias, Gunst, Jesper D., Sgaard, Ole S., Caskey, Marina, Nussenzweig, Michel C., Walker, Bruce D., Collins, David R.

Issue&Volume: 2025-12-01

Abstract: Interventions to induce lasting HIV remission are needed to obviate the requirement for lifelong antiretroviral therapy (ART). Durable post-intervention control (PIC) of viremia has been achieved in a subset of individuals following broadly neutralizing anti-HIV-1 antibody (bNAb) administration and analytical treatment interruption (ATI)1-4. Prior studies support a role for CD8+ T cells5-9 but the precise features of CD8+ T cells involved in PIC remain unclear. Here we mapped and functionally profiled CD8+ T cell responses to autologous HIV epitopes using longitudinal samples from four ATI trials in bNAb recipients. PIC was associated with superior pre-intervention HIV-specific CD8+ T cell proliferative capacity, stem cell-like memory phenotype, and recall cytotoxicity against autologous HIV peptide-pulsed CD4+ T cells. CD8+ T cell stemness was further increased following bNAb administration without emergence of new clonotypes targeting defined HLA-optimal epitopes. Multimodal single-cell analyses revealed molecular features associated with PIC and HIV-specific CD8+ T cell stemness, including signatures of metabolic fitness and reduced T cell exhaustion. These results identify immune features that precede subsequent PIC to inform the development of combination immunotherapies that will elicit durable HIV remission.

DOI: 10.1038/s41586-025-09932-w

Source: https://www.nature.com/articles/s41586-025-09932-w