Data from: Increased soluble IL-7 receptor concentrations associate with improved IL-7 therapy outcomes in SIV-infected ART-treated Rhesus macaques

The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. This study furthers our knowledge regarding the interrelationship between increased IL-7 levels and elevated sCD127 levels that may have implications for future IL-7 immunotherapeutic approaches in HIV-infected patients.

白细胞介素-7（interleukin-7, IL-7）作为免疫恢复治疗剂，已被证实在HIV感染、癌症及骨髓移植中具有显著疗效。IL-7通过膜结合型IL-7受体α（membrane-bound IL-7 receptor α, mCD127）介导其生物学活性，可提升T细胞数量与存活能力。血浆中存在其可溶性形式sCD127，本团队此前已发现HIV感染者的血浆sCD127浓度升高。进一步研究显示，血浆sCD127水平较高的患者病毒控制效果更佳，提示IL-7或sCD127可直接改善病毒学/免疫学结局。本研究针对猴免疫缺陷病毒（Simian Immunodeficiency Virus, SIV）感染且接受抗逆转录病毒（antiretroviral, ART）治疗的恒河猴的回顾性样本展开分析，探讨了细胞因子IL-7对sCD127水平的调控作用。研究采用每周集中给药方案给予IL-7，从而可评估给药前、给药期间及给药结束后的相关指标变化。在早期SIV感染阶段及ART启动后，sCD127水平均未发生明显改变。然而，IL-7治疗可使大多数受试动物的血浆sCD127浓度出现暂时性或持续性升高，该变化与T细胞数量增加同步，且与CD8阳性T细胞水平呈显著正相关。此外，以Ki67标记的增殖性CD4阳性或CD8阳性T细胞比例，亦随sCD127浓度升高而增加。最后，以BrDU标记的T细胞留存率升高与IL-7治疗组动物的高血浆sCD127水平相关。同时，病毒控制能力缺失或下降的动物，其接受IL-7治疗后血浆sCD127浓度的升高更为显著且频繁。综上，SIV感染且接受ART治疗的恒河猴的血浆sCD127水平与IL-7治疗给药相关，其中sCD127水平较高的恒河猴T细胞应答效果最佳。本研究加深了我们对IL-7水平升高与sCD127水平升高之间相互关系的认知，该发现可为未来HIV感染者的IL-7免疫治疗策略提供参考依据。