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 (T_FH) 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

次级淋巴组织中的 B 细胞滤泡是艾滋病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受感染的滤泡辅助 T (T _FH ) 细胞的滤泡之外。我们研究了天然异二聚体 IL-15 (hetIL-15) 治疗对未感染的恒河猴和自发控制 SHIV 感染至低水平慢性病毒血症的猕猴的影响。 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，LN 的多重定量图像分析（组织细胞计数）显示 B 细胞滤泡中的颗粒酶 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有望作为联合免疫治疗方案的潜在组成部分，以靶向艾滋病病毒庇护所并减少HIV-1感染者的长期病毒储存库。

试验注册： ClinicalTrials.gov NCT02452268