Nunnari Giuseppe, Pomerantz Roger J
Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Expert Opin Biol Ther. 2005 Nov;5(11):1421-6. doi: 10.1517/14712598.5.11.1421.
Highly active antiretroviral therapy (HAART), although effective in ameliorating the quality of life of HIV-1-infected individuals and their survival, has not been able to eradicate HIV-1. In fact, when HAART is interrupted, HIV-1 plasma viral load rebounds from viral reservoirs such as resting CD4+ T lymphocytes, monocytes and macrophages, remaining a major obstacle in attempting HIV eradication. Different therapeutic strategies have been attempted, such as structured treatment interruption (STI), immunotherapy (interleukin [IL]-2 and anti-CD3 antibodies [e.g., OKT3]), to try to stimulate HIV-1 out of latency along with antiretroviral intensification therapy. IL-7, a pleiotropic cytokine, bears diverse immune properties and plays a major role in T cell homeostasis. Moreover, IL-7 has recently been investigated as a possible immune adjuvant as well as a viral strain-specific inducer of HIV-1 replication. In fact, IL-7 was shown not only to be more effective than IL-2 in stimulating HIV-1 replication from resting CD4+ T lymphocytes ex vivo, but also to selectively induce a specific HIV-1 viral strain as compared with IL-2, suggesting the potential need for different viral inducers if complete eradication is to be achieved. In this present review, different immunological and virological properties of IL-7 are discussed, along with the possibility of its use as part of a combined antiretroviral-immune rationally based HIV-1 eradication approach.
高效抗逆转录病毒疗法(HAART)虽然能有效改善HIV-1感染者的生活质量并延长其生存期,但尚未能够根除HIV-1。事实上,当HAART中断时,HIV-1血浆病毒载量会从静止的CD4+T淋巴细胞、单核细胞和巨噬细胞等病毒储存库中反弹,这仍然是试图根除HIV的主要障碍。人们尝试了不同的治疗策略,如结构化治疗中断(STI)、免疫疗法(白细胞介素[IL]-2和抗CD3抗体[如OKT3]),试图在强化抗逆转录病毒治疗的同时刺激HIV-1从潜伏状态中出来。IL-7是一种多效性细胞因子,具有多种免疫特性,在T细胞稳态中起主要作用。此外,最近对IL-7作为一种可能的免疫佐剂以及HIV-1复制的病毒株特异性诱导剂进行了研究。事实上,研究表明,IL-7不仅在体外刺激静止CD4+T淋巴细胞中的HIV-1复制方面比IL-2更有效,而且与IL-2相比能选择性地诱导特定的HIV-1病毒株,这表明如果要实现完全根除,可能需要不同的病毒诱导剂。在本综述中,讨论了IL-7的不同免疫和病毒学特性,以及将其用作基于抗逆转录病毒-免疫联合合理方法根除HIV-1一部分的可能性。