Furler Robert L, Newcombe Kevin L, Del Rio Estrada Perla M, Reyes-Terán Gustavo, Uittenbogaart Christel H, Nixon Douglas F
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York.
Departmento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas," CDMX, Mexico DF, Mexico.
AIDS Res Hum Retroviruses. 2019 Nov/Dec;35(11-12):1148-1159. doi: 10.1089/AID.2019.0156. Epub 2019 Oct 7.
Impaired immunity is a common symptom of aging and advanced Human Immunodeficiency Virus type 1 (HIV-1) disease. In both diseases, a decline in lymphocytic function and cellularity leads to ineffective adaptive immune responses to opportunistic infections and vaccinations. Furthermore, despite sustained myeloid cellularity there is a background of chronic immune activation and a decrease in innate immune function in aging. In HIV-1 disease, myeloid cellularity is often more skewed than in normal aging, but similar chronic activation and innate immune dysfunction typically arise. Similarities between aging and HIV-1 infection have led to several investigations into HIV-1-mediated aging of the immune system. In this article, we review various studies that report alterations of leukocyte number and function during aging, and compare those alterations with those observed during progressive HIV-1 disease. We pay particular attention to changes within lymphoid tissue microenvironments and how histoarchitectural changes seen in these two diseases affect immunity. As we review various immune compartments including peripheral blood as well as primary and secondary lymphoid organs, common themes arise that help explain the decline of immunity in the elderly and in HIV-1-infected individuals with advanced disease. In both conditions, lymphoid tissues often show signs of histoarchitectural deterioration through fat accumulation and/or fibrosis. These structural changes can be attributed to a loss of communication between leukocytes and the surrounding stromal cells that produce the extracellular matrix components and growth factors necessary for cell migration, cell proliferation, and lymphoid tissue function. Despite the common general impairment of immunity in aging and HIV-1 progression, deterioration of immunity is caused by distinct mechanisms at the cellular and tissue levels in these two diseases.
免疫功能受损是衰老和晚期人类免疫缺陷病毒1型（HIV-1）疾病的常见症状。在这两种疾病中，淋巴细胞功能和细胞数量的下降导致对机会性感染和疫苗接种的适应性免疫反应无效。此外，尽管髓细胞数量持续存在，但衰老过程中存在慢性免疫激活背景和先天免疫功能下降。在HIV-1疾病中，髓细胞数量往往比正常衰老时更不均衡，但通常也会出现类似的慢性激活和先天免疫功能障碍。衰老与HIV-1感染之间的相似性引发了多项关于HIV-1介导的免疫系统衰老的研究。在本文中，我们回顾了各种报告衰老过程中白细胞数量和功能变化的研究，并将这些变化与进行性HIV-1疾病期间观察到的变化进行比较。我们特别关注淋巴组织微环境中的变化，以及这两种疾病中观察到的组织架构变化如何影响免疫。当我们回顾包括外周血以及一级和二级淋巴器官在内的各种免疫区室时，出现了一些共同主题，有助于解释老年人和晚期HIV-1感染个体免疫力下降的原因。在这两种情况下，淋巴组织通常会通过脂肪堆积和/或纤维化表现出组织架构恶化的迹象。这些结构变化可归因于白细胞与周围基质细胞之间的通讯丧失，这些基质细胞产生细胞迁移、细胞增殖和淋巴组织功能所需的细胞外基质成分和生长因子。尽管衰老和HIV-1进展中普遍存在免疫功能受损，但这两种疾病在细胞和组织水平上，免疫功能恶化是由不同机制引起的。
