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Old age-associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-05-04 , DOI: 10.1002/eji.201948261 Manju Namdeo 1 , Ramesh Kandel 2 , Prabhakar Kumar Thakur 2 , Anant Mohan 3 , Aparajit Ballav Dey 2 , Dipendra Kumar Mitra 1
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-05-04 , DOI: 10.1002/eji.201948261 Manju Namdeo 1 , Ramesh Kandel 2 , Prabhakar Kumar Thakur 2 , Anant Mohan 3 , Aparajit Ballav Dey 2 , Dipendra Kumar Mitra 1
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Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T‐cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age‐associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N‐acetyl‐cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN‐γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti‐tubercular treatment. We could rescue Myobacterium tuberculosis‐specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co‐culture experiments, blocking experiments using antibodies against IL‐10, TGF‐β, and programmed death‐1 (PD‐1) as well as NAC supplementation. We report old age‐associated enrichment of Treg cells and suppression of M. tuberculosis‐specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.
中文翻译：
老年肺结核患者外周血T调节细胞的富集和氧化还原状态的改变。
衰老影响对包括结核病（TB）在内的各种传染病的易感性和预后。尽管老年人的T细胞功能和免疫力受到损害，但老年人中结核病高发的机制仍然未知。在这里，我们评估了与年龄相关的免疫改变，尤其是肺结核患者的效应子和Treg反应。我们还评估了氧化还原状态及其对N乙酰半胱氨酸（NAC）调节对老年结核病的影响。老年结核病患者中观察到较高的Treg细胞频率和减少的IFN-γ阳性T细胞。Treg细胞数量的增加与细菌负荷（即疾病的严重程度）紧密相关；对成功的抗结核治疗反应明显下降。我们可以营救通过多种体外方法对结核分枝杆菌特异的效应T细胞（Th1）做出反应，例如Treg细胞耗竭和共培养实验，使用针对IL-10，TGF-β的抗体和程序性死亡1（PD- 1）以及NAC补充。我们报告了与年龄相关的Treg细胞的富集和结核分枝杆菌特异性效应子T（Th1）细胞免疫反应的抑制。监测老年患者的这些免疫失衡可能通过选择性靶向Treg细胞和/或通过补充NAC优化氧化还原状态来帮助增强免疫力。
更新日期：2020-05-04
中文翻译：
老年肺结核患者外周血T调节细胞的富集和氧化还原状态的改变。
衰老影响对包括结核病（TB）在内的各种传染病的易感性和预后。尽管老年人的T细胞功能和免疫力受到损害，但老年人中结核病高发的机制仍然未知。在这里，我们评估了与年龄相关的免疫改变，尤其是肺结核患者的效应子和Treg反应。我们还评估了氧化还原状态及其对N乙酰半胱氨酸（NAC）调节对老年结核病的影响。老年结核病患者中观察到较高的Treg细胞频率和减少的IFN-γ阳性T细胞。Treg细胞数量的增加与细菌负荷（即疾病的严重程度）紧密相关；对成功的抗结核治疗反应明显下降。我们可以营救通过多种体外方法对结核分枝杆菌特异的效应T细胞（Th1）做出反应，例如Treg细胞耗竭和共培养实验，使用针对IL-10，TGF-β的抗体和程序性死亡1（PD- 1）以及NAC补充。我们报告了与年龄相关的Treg细胞的富集和结核分枝杆菌特异性效应子T（Th1）细胞免疫反应的抑制。监测老年患者的这些免疫失衡可能通过选择性靶向Treg细胞和/或通过补充NAC优化氧化还原状态来帮助增强免疫力。
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