School of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom.
Laboratory of Clinical Immunology, Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
J Infect Dis. 2018 May 25;217(12):1997-2007. doi: 10.1093/infdis/jiy096.
Interleukin (IL)-7 promotes the generation, expansion, and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy, and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown.
In this study, we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens. After short-term exposure to IL-7, we measured PBMC responses to antigens derived from pathogens, such as Mycobacterium tuberculosis, Candida albicans, and cytomegalovirus, and to the superantigen Staphylococcus aureus enterotoxin B.
We found that IL-7 favored the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific interferon-γ, IL-2, and tumor necrosis factor recall responses.
Our findings indicate that IL-7 unveils and supports reactivation of pathogen-specific T cells with possible diagnostic, prognostic, and therapeutic significance of clinical value, especially in conditions of pathogen persistence and chronic infection.
白细胞介素(IL)-7 可促进记忆 T 细胞的生成、扩增和存活。先前的小鼠和人类研究表明,IL-7 可支持淋巴缺失情况下免疫细胞的重建,扩增用于过继免疫治疗的肿瘤反应性 T 细胞,并增强自身反应性 T 细胞的效应细胞因子表达。病原体反应性 T 细胞是否也受益于 IL-7 的暴露尚不清楚。
在本研究中,我们调查了来自感染各种地方性病原体的患者外周血单核细胞(PBMC)培养物中的这一问题。在短期暴露于 IL-7 后,我们测量了 PBMC 对源自病原体的抗原(如结核分枝杆菌、白色念珠菌和巨细胞病毒)和金黄色葡萄球菌肠毒素 B 的超抗原的反应。
我们发现,IL-7 通过促进病原体特异性干扰素-γ、IL-2 和肿瘤坏死因子回忆反应,有利于病原体反应性 CD4 T 细胞的扩增,在某些情况下还可揭示这些细胞。
我们的研究结果表明,IL-7 可揭示并支持病原体特异性 T 细胞的重新激活,这可能具有诊断、预后和治疗的临床价值,特别是在病原体持续存在和慢性感染的情况下。