Ford Bart N, Teague T Kent, Bayouth Morgan, Yolken Robert H, Bodurka Jerzy, Irwin Michael R, Paulus Martin P, Savitz Jonathan
Laureate Institute for Brain Research, Tulsa, OK, USA; Department of Biological Science, The University of Tulsa, Tulsa, OK, USA.
Departments of Surgery and Psychiatry, University of Oklahoma School of Community Medicine, Tulsa, OK, USA; Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA; Integrative Immunology Center, University of Oklahoma School of Community Medicine, Tulsa, OK, USA.
Brain Behav Immun. 2020 Jul;87:795-803. doi: 10.1016/j.bbi.2020.03.013. Epub 2020 Mar 21.
Major depressive disorder (MDD) is associated with physiological changes commonly observed with increasing age, such as inflammation and impaired immune function. Age-related impaired adaptive immunity is characterized by the loss of naive T-cells and the reciprocal accumulation of memory T-cells together with the loss of T-cell co-stimulatory molecules. Additionally, the presence and activity of cytomegalovirus (CMV) alters the architecture of the T-cell compartment in a manner consistent with premature aging. Because CMV is also thought to reactivate with psychological stress, this study tested whether MDD influences age-related phenotypes of T-cell populations in the context of CMV infection in young and middle-aged adults. Morning blood samples from volunteers with a DSM-IV diagnosis of MDD (n = 98, mean age(SD) = 36(10) years, 74.5% female, 57.1% CMV) and comparison controls (n = 98, mean age(SD) = 34(10) years, 68.4% female, 51.0% CMV) were evaluated for CMV IgG antibody status and the distribution of late differentiated (CD27CD28) cells within CD4 and CD8 T-cell subsets, i.e. naive (CCR7CD45RA), effector memory (EM, CCR7CD45RA), central memory (CM, CCR7CD45RA) and effector memory cells re-expressing CD45RA (EMRA, CCR7CD45RA). Mixed linear regression models controlling for age, sex, ethnicity and flow cytometry batch showed that CMV seropositivity was associated with a reduction in naive T-cells, expansion of EMRA T-cells, and a greater percent distribution of CD27CD28 cells within CD4 and CD8 memory T-cell subsets (p's < 0.004), but there was no significant effect of MDD, nor any significant interaction between CMV and diagnosis. Unexpectedly, depressed men were less likely to be CMV and depressed women were more likely to be CMV than sex-matched controls suggesting a possible interaction between sex and MDD on CMV susceptibility, but this three-way interaction did not significantly affect the T-cell subtypes. Our findings suggest that depression in young and middle-aged adults does not prematurely advance aging of the T-cell compartment independently of CMV, but there may be significant sex-specific effects on adaptive immunity that warrant further investigation.
重度抑郁症（MDD）与随着年龄增长而常见的生理变化相关，如炎症和免疫功能受损。与年龄相关的适应性免疫受损的特征是初始T细胞的丧失以及记忆T细胞的相应积累，同时伴有T细胞共刺激分子的丧失。此外，巨细胞病毒（CMV）的存在和活性以与早衰一致的方式改变了T细胞区室的结构。由于CMV也被认为会因心理压力而重新激活，因此本研究测试了在年轻和中年成年人的CMV感染背景下，MDD是否会影响T细胞群体与年龄相关的表型。对符合《精神疾病诊断与统计手册》第四版（DSM-IV）诊断标准的MDD志愿者（n = 98，平均年龄（标准差）= 36（10）岁，74.5%为女性，57.1%感染CMV）和对照者（n = 98，平均年龄（标准差）= 34（10）岁，68.4%为女性，51.0%感染CMV）的清晨血样进行评估，检测CMV IgG抗体状态以及CD4和CD8 T细胞亚群中晚期分化（CD27-CD28-）细胞的分布，即初始（CCR7+CD45RA+）、效应记忆（EM，CCR7-CD45RA-）、中枢记忆（CM，CCR7+CD45RA-）和重新表达CD45RA的效应记忆细胞（EMRA，CCR7-CD45RA-）。控制年龄、性别、种族和流式细胞术批次的混合线性回归模型显示，CMV血清阳性与初始T细胞减少、EMRA T细胞扩增以及CD4和CD8记忆T细胞亚群中CD27-CD28-细胞的百分比分布增加相关（p值<0.004），但MDD没有显著影响，CMV与诊断之间也没有显著的相互作用。出乎意料的是，与性别匹配的对照组相比，抑郁男性感染CMV的可能性较小，而抑郁女性感染CMV的可能性较大，这表明性别与MDD在CMV易感性上可能存在相互作用，但这种三方相互作用并未显著影响T细胞亚型。我们的研究结果表明，年轻和中年成年人的抑郁症不会独立于CMV而过早地促进T细胞区室的衰老，但可能对适应性免疫有显著的性别特异性影响，值得进一步研究。
