Kumar Nathella Pavan, Moideen Kadar, George Parakkal Jovvian, Dolla Chandrakumar, Kumaran Paul, Babu Subash
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
National Institute for Research in Tuberculosis, Chennai, India.
Eur J Immunol. 2016 Feb;46(2):390-9. doi: 10.1002/eji.201545973. Epub 2015 Nov 19.
Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF-β, since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease.
2型糖尿病（DM）是活动性肺结核（TB）发病的一个危险因素，尽管其在潜伏性结核（LTB）的结核诱导反应中的作用尚不完全清楚。由于Th1、Th2和Th17反应在LTB免疫中很重要，我们推测合并DM可能会改变这些CD4(+) T细胞亚群的功能。为此，我们检测了LTB-DM个体全血中分枝杆菌诱导的免疫反应，并将其与无DM个体（LTB-NDM）的反应进行比较。LTB-DM的T细胞反应特征为，在基线时以及用分枝杆菌抗原——纯化蛋白衍生物、早期分泌抗原-6和培养滤液蛋白-10刺激后，单功能和双功能CD4(+) Th1、Th2和Th17细胞的频率降低。这种调节至少部分依赖于IL-10和TGF-β，因为中和这两种细胞因子中的任何一种都会导致LTB-DM个体而非LTB个体中Th1和Th2细胞的频率显著增加，但Th17细胞的频率没有增加。因此，LTB-DM的特征是Th1、Th2和Th17细胞的频率降低，这表明DM会改变潜伏性结核中的免疫反应，导致保护性CD4(+) T细胞反应的诱导不理想，从而为增加活动性疾病易感性提供了一种潜在机制。
