Texas Biomedical Institute, San Antonio, TX, United States of America; The University of Texas Health Science Center of San Antonio, San Antonio, TX, United States of America.
Texas Biomedical Institute, San Antonio, TX, United States of America.
Exp Gerontol. 2022 Oct 1;167:111904. doi: 10.1016/j.exger.2022.111904. Epub 2022 Jul 30.
Age-related changes in the immune system increase susceptibility to infectious diseases. Vaccines are an important tool to prevent infection or boost immunological memory; however, vaccines are less effective in aged individuals. In order to protect our aging population from the threat of infectious diseases, we must gain a better understanding of age-related alterations in the immune response at the site of infection. The lung is one site of frequent infection in older individuals. In this study, we expanded on our previous work to study vaccine-induced immune responses in the local lung environment in a pilot study of aged rhesus macaques. To do this, we developed an in vivo model to probe recall responses to tuberculin challenge in the lungs 8 weeks and 16 weeks post-Mycobacterium bovis BCG vaccination by performing targeted bronchoalveolar lavages. In parallel, we determined peripheral blood responses in vaccinated animals to compare systemic and local tissue responses to tuberculin challenge. We found that following lung tuberculin challenge 8 weeks post-vaccination, aged animals had reduced T cell responses, particularly within the CD8 T cell compartment. Aged animals had decreased CD8 effector and memory T cell recall responses and less activated CD8 T cells. This diminished lung CD8 T cell response in aged animals was maintained over time. Despite changes in the CD8 T cell compartment, lung CD4 T cell responses were similar between age groups. In the peripheral blood, we observed age-related changes in immune cell populations and plasma levels of immune mediators that were present prior to vaccination. Lastly, we found that peripheral blood mononuclear cells from aged BCG-vaccinated animals were functional in their response to antigen stimulation, behaving in a similar manner to those from their adult counterparts. These systemic observations were similar to those found in our previous study of BCG-vaccinated baboons, supporting the notion that tissue immune responses, and not systemic responses, to vaccination and challenge are impaired with age. These findings expand on our previous work to show that in addition to the skin, age-related changes in the lung environment impact recall immune responses to vaccination and challenge. The impact of age on local tissue responses to infectious challenge should be accounted for in the development of therapeutics or medical interventions aimed at boosting immune recall responses of aged individuals.
随着年龄的增长，免疫系统会发生变化，从而使人更容易感染传染病。疫苗是预防感染或增强免疫记忆的重要工具；然而，疫苗在老年人中的效果较差。为了保护我们的老年人口免受传染病的威胁，我们必须更好地了解感染部位与年龄相关的免疫反应变化。肺部是老年人经常感染的部位之一。在这项研究中，我们在之前对老年恒河猴的研究基础上进一步研究了肺部局部感染环境中疫苗诱导的免疫反应。为此，我们通过进行靶向支气管肺泡灌洗，建立了一种体内模型来探测牛结核分枝杆菌卡介苗接种后 8 周和 16 周肺部结核菌素挑战的回忆反应。同时，我们还测定了接种疫苗动物的外周血反应，以比较系统和局部组织对结核菌素挑战的反应。我们发现，在接种疫苗后 8 周肺部结核菌素挑战后，老年动物的 T 细胞反应减少，特别是在 CD8 T 细胞群中。老年动物的 CD8 效应和记忆 T 细胞回忆反应减少，CD8 T 细胞激活减少。老年动物的这种肺部 CD8 T 细胞反应随时间而持续。尽管 CD8 T 细胞群发生了变化，但两组之间的肺部 CD4 T 细胞反应相似。在外周血中，我们观察到免疫细胞群和免疫介质的血浆水平在接种疫苗前就存在与年龄相关的变化。最后，我们发现，来自老年卡介苗接种动物的外周血单核细胞对抗原刺激的反应具有功能性，其行为与成年动物相似。这些系统观察结果与我们之前对卡介苗接种狒狒的研究结果相似，支持这样一种观点，即疫苗接种和挑战后的组织免疫反应而不是系统反应随着年龄的增长而受损。这些发现扩展了我们之前的工作，表明除了皮肤外，肺部环境与年龄相关的变化会影响对疫苗和挑战的回忆性免疫反应。在开发旨在增强老年人免疫记忆反应的治疗方法或医疗干预措施时，应考虑年龄对局部组织对感染性挑战的反应的影响。
