奥地利维也纳医科大学Georg Stary、Simona Saluzzo等研究人员合作发现，HIV感染者延迟抗逆转录病毒治疗会导致皮肤和粘膜常驻记忆T细胞的不可逆耗竭。该研究于2021年11月22日在线发表于国际一流学术期刊《免疫》。

研究人员发现，皮肤CD4⁺组织驻留记忆T（Trim）细胞在HIV感染后被耗尽，只有在早期抗逆转录病毒治疗（ART）开始时才能得到补充。早期ART后的TCR克隆分析表明，重建CD4⁺ Trm细胞有一个系统性的来源。接受晚期ART治疗的艾滋病携带者（PLWH）单细胞RNA测序显示了CXCR3⁺ Trm细胞的损失和耐受性的皮肤免疫环境。人乳头瘤病毒诱导的癌前病变活检显示，PLWH与HIV个体相比，粘膜中CXCR3⁺ Trm细胞的频率降低。

这些结果显示出接受晚期ART治疗的PLWH中，局限于皮肤和粘膜的CXCR3⁺ Trm细胞的不可逆丧失，这可能是HPV相关癌症发展的一个诱发因素。

据介绍，尽管在ART后CD4⁺ T细胞得到了系统的重建，但PLWH发生皮肤和粘膜恶性肿瘤的风险却在增加。HIV慢性组织相关免疫缺陷的潜在机制尚不清楚。

附：英文原文

Title: Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells

Author: Simona Saluzzo, Ram Vinay Pandey, Laura Marie Gail, Ruth Dingelmaier-Hovorka, Lisa Kleissl, Lisa Shaw, Brbel Reininger, Denise Atzmüller, Johanna Strobl, Veronique Touzeau-Rmer, Andrea Beer, Clement Staud, Armin Rieger, Matthias Farlik, Wolfgang Weninger, Georg Stingl, Georg Stary

Issue&Volume: 2021-11-22

Abstract: People living with HIV (PLWH) are at increased risk for developing skin and mucosalmalignancies despite systemic reconstitution of CD4+ T cells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-relatedimmunodeficiency in HIV is unclear. We found that skin CD4+ tissue-resident memory T (Trm) cells were depleted after HIV infection and replenishedonly upon early ART initiation. TCR clonal analysis following early ART suggesteda systemic origin for reconstituting CD4+ Trm cells. Single-cell RNA sequencing in PLWH that received late ART treatment revealeda loss of CXCR3+ Trm cells and a tolerogenic skin immune environment. Human papilloma virus-inducedprecancerous lesion biopsies showed reduced CXCR3+ Trm cell frequencies in the mucosa in PLWH versus HIV individuals. These results reveal an irreversible loss of CXCR3+ Trm cells confined to skin and mucosa in PLWH who received late ART treatment, whichmay be a precipitating factor in the development of HPV-related cancer.

DOI: 10.1016/j.immuni.2021.10.021

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00459-3