用天然异二聚体 IL-15 治疗可增加细胞毒性淋巴细胞并减少淋巴结中的 SHIV RNA。

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes.

机构信息

Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.

出版信息

PLoS Pathog. 2018 Feb 23;14(2):e1006902. doi: 10.1371/journal.ppat.1006902. eCollection 2018 Feb.

UNLABELLED

B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry) of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02452268.

未标记

次级淋巴组织中的 B 细胞滤泡代表 AIDS 病毒的免疫特权避难所，部分原因是细胞毒性 CD8+T 细胞大多被排除在含有感染的滤泡辅助性 T 细胞（TFH）的滤泡之外。我们研究了天然异二聚体 IL-15（hetIL-15）治疗对未感染恒河猴和对自发性控制 SHIV 感染至慢性病毒血症低水平的恒河猴的影响。hetIL-15 增加了血液、粘膜部位和淋巴结中具有高颗粒酶 B 含量的效应 CD8+T 淋巴细胞，包括 LN 中的病毒特异性 MHC-肽四聚体+CD8+细胞。hetIL-15 治疗后，对 LN 进行的多重定量图像分析（组织细胞计量术）显示 B 细胞滤泡中颗粒酶 B+T 细胞数量增加，血浆和 LN 中的 SHIV RNA 减少。基于这些特性，hetIL-15 有望成为联合免疫治疗方案的潜在成分，以靶向 AIDS 病毒避难所并减少 HIV-1 感染个体中的长期病毒储存库。