Clinical Immunology Department, Center of Molecular Immunology, 216 St, corner 15, PO box 16040, Atabey, Havana, Cuba.
Ludwig Cancer Research Center and Department of Oncology, University of Lausanne (UNIL), CH-1066 Epalinges, Switzerland.
Exp Gerontol. 2019 Sep;124:110633. doi: 10.1016/j.exger.2019.110633. Epub 2019 Jun 14.
The changes that occur in the immune system with aging are commonly termed immunosenescence. Immunosenescence affects almost all components and functions of the immune response. The most commonly described change is a decrease in numbers and proportions of naïve T cells combined with the increase of terminally differentiated T lymphocytes, mainly affecting CD8+ T cells. The changes in the naïve T cell compartment are principally attributed to thymic involution and lifelong chronic antigen stimulation, among other triggers. Several strategies such as hormonal products, thymic peptides, or cytokines have been proposed for the restoration of the immune system. Here we show the effects of Biomodulina T (BT) on several populations of the immune system when administered to elderly patients diagnosed with recurrent respiratory infections. BT is a polypeptide fraction of bovine thymus, a Cuban product that obtained sanitary registration in 1994 for its immunomodulatory effects. We found that CD4+ naïve T, CD8+ stem cell-like memory (SCM) T, CD4+ recent thymic emigrants (RTE) T and CD4+ CD31+ naïve T cells increased with the administration of BT, whereas CD4+ and CD8+ T cells expressing PD1 decreased after the treatment with BT. Additionally, the proliferative capacity of CD4+ T cells measured by Ki67 expression, and the CD4+ T cell ability to produce IFN-γ were also improved by BT. Moreover, BT did not increase CD4+ Tregs. Altogether, these findings suggest that BT administration is a promising strategy for immune restoration in elderly patients and improvement of immunotherapeutic potential in cancer patients.
随着年龄的增长，免疫系统发生的变化通常被称为免疫衰老。免疫衰老几乎影响免疫反应的所有组成部分和功能。最常描述的变化是幼稚 T 细胞数量和比例减少，同时终末分化的 T 淋巴细胞增加，主要影响 CD8+ T 细胞。幼稚 T 细胞区室的变化主要归因于胸腺萎缩和终生慢性抗原刺激等触发因素。已经提出了几种策略，如激素产品、胸腺肽或细胞因子，以恢复免疫系统。在这里，我们展示了 Biomodulina T（BT）对老年患者反复呼吸道感染时免疫系统几个群体的影响。BT 是牛胸腺的多肽片段，是一种古巴产品，1994 年因其免疫调节作用获得了卫生注册。我们发现，BT 给药后 CD4+幼稚 T、CD8+干细胞样记忆（SCM）T、CD4+近期胸腺迁出（RTE）T 和 CD4+CD31+幼稚 T 细胞增加，而表达 PD1 的 CD4+和 CD8+T 细胞减少。此外，通过 Ki67 表达测量的 CD4+T 细胞的增殖能力以及 CD4+T 细胞产生 IFN-γ的能力也通过 BT 得到改善。此外，BT 并没有增加 CD4+Treg。总之，这些发现表明 BT 给药是老年患者免疫恢复和改善癌症患者免疫治疗潜力的有前途的策略。
