Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. In this pilot study, we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test in two adult and two aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. In vitro, aged peripheral blood mononuclear cells had increased migration and functional responses to antigen-specific stimulation, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.

中文翻译：

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接种 BCG 的牛分枝杆菌狒狒对结核菌素皮肤攻击的局部免疫反应：对年轻和年老动物的初步研究


65岁以上的人极易感染传染病，占该年龄段死亡人数的三分之一。疫苗是对抗感染的主要工具，但对老年人群来说效果较差。虽然许多团体的目标是通过研究疫苗引起的老年人外周血反应来解决这个问题，但我们实验室和其他实验室的工作表明，组织部位和外周组织对疫苗和感染挑战的免疫反应可能不同。在这项初步研究中，我们在两只成年狒狒和两只老年狒狒身上建立了牛分枝杆菌卡介苗接种和结核菌素皮试的体内迟发型超敏反应模型。疫苗接种会产生卡介苗特异性免疫细胞，这些免疫细胞在结核菌素攻击后被募集到皮肤上。我们通过在结核菌素注射部位周围进行皮肤穿刺活检来测试短期回忆反应（疫苗接种后 8 周）和长期回忆反应（疫苗接种后 25 周）。在短期回忆反应中，我们发现与成年狒狒皮肤相比，TST 攻击部位的老年狒狒皮肤氧化增加，免疫蛋白产生减少。成年动物和老年动物对结核菌素的长期反应的差异正常化。在体外，衰老的外周血单核细胞对抗原特异性刺激的迁移和功能反应增加，这表明体内组织中与年龄相关的变化损害了对抗原攻击的衰老免疫回忆反应。这些发现强调了局部组织环境与年龄相关的变化对记忆回忆反应的影响，这可能更广泛地应用于其他组织的研究。 此外，这些发现应该在未来的研究中得到考虑，这些研究旨在了解和改善对疫苗接种和组织挑战的衰老免疫反应。