Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV− and CMV+ groups. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV− persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

中文翻译：

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体重指数对人骨髓中适应性免疫细胞的影响。

肥胖与慢性炎症和氧化应激有关。这两种情况在年龄相关疾病的发病机制中都起着决定性作用，例如免疫衰老。脂肪组织可以通过分泌影响免疫细胞表型的分子来调节免疫系统的功能。骨髓 (BM) 在维持具有抗原的适应性免疫细胞中的重要性已在小鼠中得到证实。最近，一些研究小组研究了人类 BM 中效应/记忆 T 细胞的存活率。尽管如此，高体重指数 (BMI) 是否会影响 BM 中的免疫细胞以及支持维持这些细胞的分子的产生尚不清楚。使用流式细胞仪，在从不同 BMI 的人获得的成对的 BM 和 PB 样本中测量免疫细胞群的频率和表型。此外，评估了BM细胞因子的表达。还考虑了巨细胞病毒 (CMV) 对 T 细胞亚群的影响，将供体分为 CMV- 和 CMV+ 组。我们的研究表明，增加的 BMI 可能会影响 BM 中适应性免疫细胞的维持和表型。虽然支持高度分化 T 细胞存活的 IL-15 和 IL-6 的 BM 水平以及超重人群中的氧自由基增加，但 CD8+ T 细胞产生的 IFNγ 和 TNF 减少。此外，CMV-人BM中B细胞和CD4+ T细胞的频率与BMI呈正相关。最后，几个T细胞亚群的频率，以及这些亚群中衰老/衰竭标志物的表达受到 BMI 的影响。特别是，超重者的真实记忆 T 细胞水平可能会降低。我们的工作表明，除了衰老和 CMV 之外，肥胖可能是适应性免疫细胞免疫衰老的另一个风险因素。代谢干预可能有助于改善老年人免疫系统的健康状况。