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 (CD27-CD28-) cells within CD4+ and CD8+ T-cell subsets, i.e. naive (CCR7+CD45RA+), effector memory (EM, CCR7-CD45RA-), central memory (CM, CCR7+CD45RA-) and effector memory cells re-expressing CD45RA (EMRA, CCR7-CD45RA+). 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 CD27-CD28- 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.

中文翻译：

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巨细胞病毒感染个体中 T 细胞共刺激分子的非诊断性丢失

重度抑郁症 (MDD) 与随着年龄增长而常见的生理变化有关，例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 细胞的丧失和记忆 T 细胞的相互积累以及 T 细胞共刺激分子的丧失。此外，巨细胞病毒 (CMV) 的存在和活性以与过早衰老一致的方式改变了 T 细胞室的结构。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 MDD 是否会在中青年 CMV 感染的情况下影响 T 细胞群的年龄相关表型。来自 DSM-IV 诊断为 MDD 的志愿者的早晨血液样本（n=98，平均年龄（sd）=36（10）岁，74.5% 女性，57。1% CMV+）和比较对照（n=98，平均年龄（sd）=34（10）岁，68.4% 女性，51.0% CMV+）评估 CMV IgG 抗体状态和晚期分化（CD27-CD28- ) CD4+ 和 CD8+ T 细胞亚群中的细胞，即幼稚 (CCR7+CD45RA+)、效应记忆细胞 (EM, CCR7-CD45RA-)、中央记忆细胞 (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表明，CMV 血清阳性与幼稚 T 细胞减少、EMRA T 细胞扩增以及 CD4+ 内 CD27-CD28-细胞的更大百分比分布有关和 CD8+ 记忆 T 细胞亚群（p<0.004），但 MDD 没有显着影响，CMV 和诊断之间也没有任何显着的相互作用。不料，与性别匹配的对照相比，抑郁男性不太可能是 CMV+，而抑郁女性更可能是 CMV+，这表明性别和 MDD 之间可能在 CMV 易感性上存在相互作用，但这种三向相互作用并未显着影响 T 细胞亚型。我们的研究结果表明，年轻人和中年人的抑郁症不会独立于 CMV 过早地促进 T 细胞室的老化，但可能对适应性免疫存在显着的性别特异性影响，值得进一步研究。