Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Critical Care Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
JCI Insight. 2019 Sep 19;4(18):130664. doi: 10.1172/jci.insight.130664.
BACKGROUNDHIV-infected patients with poor virologic control and multidrug-resistant virus have limited therapeutic options. The current study was undertaken to evaluate the safety, immunologic effects, and antiviral activity of peripheral lymphocytes transferred from an elite controller, whose immune system is able to control viral replication without antiretroviral medications, to an HLA-B*2705-matched progressor.METHODSApproximately 22 billion cells were collected from an elite controller by lymphapheresis and infused within 6 hours into a recipient with a preinfusion CD4+ T cell count of 10 cells/μL (1%) and HIV plasma viral load of 114,993 copies/mL.RESULTSDonor cells were cleared from the recipient's peripheral blood by day 8. A transient decrease in viral load to 58,421 (day 3) was followed by a rebound to 702,972 (day 6) before returning to baseline values by day 8. The decreased viral load was temporally associated with peak levels of donor T cells, including CD8+ T cells that had high levels of expression of Ki67, perforin, and granzyme B. Notably, recipient CD8+ T cells also showed increased expression of these markers, especially in HIV-specific tetramer-positive cells.CONCLUSIONThese results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways.TRIAL REGISTRATIONClinicalTrials.gov NCT00559416.FUNDINGIntramural Research Programs of the US NIH Clinical Center and the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute.
HIV 感染患者的病毒学控制不佳且存在多种耐药病毒,其治疗选择有限。本研究旨在评估从一名精英控制者(其免疫系统能够在没有抗逆转录病毒药物的情况下控制病毒复制)转移外周淋巴细胞的安全性、免疫效果和抗病毒活性,该控制者的 HLA-B*2705 与一名匹配的进展者相匹配。
通过淋巴清除术从精英控制器中收集了大约 220 亿个细胞,并在输注前 CD4+T 细胞计数为 10 个/μL(1%)和 HIV 血浆病毒载量为 114993 拷贝/mL 的情况下,在 6 小时内将其输注到接受者体内。
供体细胞在接受者的外周血中于第 8 天被清除。病毒载量先短暂下降至 58421(第 3 天),然后反弹至 702972(第 6 天),在第 8 天恢复基线值。病毒载量的下降与供体细胞,包括高水平表达 Ki67、穿孔素和颗粒酶 B 的 CD8+T 细胞的峰值水平呈时间相关性。值得注意的是,受者 CD8+T 细胞也表现出这些标记物的表达增加,特别是在 HIV 特异性四聚体阳性细胞中。
这些结果表明,从 HIV 感染的精英控制者向进展性疾病的 HIV 感染患者转移淋巴细胞可能能够以积极和消极的方式干扰接受者的免疫系统。
ClinicalTrials.gov NCT00559416。
美国国立卫生研究院临床中心和国家过敏和传染病研究所(NIAID)的内部研究计划;国家癌症研究所。