CD4+和CD8+T细胞及线粒体质量与抑郁症的相关性

doi:10.3969/j.issn.1006-7795.2025.06.020

首都医科大学学报 ›› 2025, Vol. 46 ›› Issue (6): 1118-1125.doi: 10.3969/j.issn.1006-7795.2025.06.020

CD4⁺和CD8⁺T细胞及线粒体质量与抑郁症的相关性

孙雪娇^1,2，刘彦茹³，王志仁^2*

1.华北理工大学精神与心理学院，河北唐山 063200；2.北京回龙观医院科技处，北京 100096；3.首都医科大学附属北京儿童医院心身医学科，北京 100045

收稿日期:2025-02-21 修回日期:2025-10-06 出版日期:2025-12-21 发布日期:2025-12-19
通讯作者: 王志仁 E-mail:zhiren75@163.com
基金资助:
首都卫生发展科研专项自主创新项目（首发2022-2-2133）。

Correlation between CD4⁺ and CD8⁺ T cells, mitochondrial mass, and depression

Sun Xuejiao^1，2， Liu Yanru ³，Wang Zhiren ^2*

1. School of Psychiatry and Psychology, North China University of Science and Technology, Tangshan 063200，Hebei Province ,China；2.Department of Science and Technology,Beijing Huilongguan Hospital, Beijing 100096, China；3.Department of Psychosomatic Medicine, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China

Received:2025-02-21 Revised:2025-10-06 Online:2025-12-21 Published:2025-12-19
Supported by:
This study was supported by the Capital Health Development Research Special-Independent Innovation Program (2022-2-2133).

摘要/Abstract

摘要： 目的探讨抑郁症患者外周血中CD4⁺、CD8⁺T细胞数量及线粒体质量（mean fluorescence intensity，MFI）变化特征，分析其与抑郁严重程度［汉密尔顿抑郁量表（Hamilton Depression Rating Scale, HAMD）评分］的关系。方法纳入31例抑郁症患者与50例健康对照者，采用流式细胞术检测T细胞数量及线粒体质量。比较采用Welch t检验与Mann-Whitney U检验，相关性分析采用Pearson法并行FDR校正，多元线性回归用于预测HAMD评分。结果抑郁组CD4⁺、CD8⁺ T细胞数量与线粒体质量均低于对照组，差异有统计学意义（P<0.01），HAMD评分与CD8⁺线粒体质量呈最强负相关（R=－0.570，P<0.001）。多元回归显示，CD8⁺线粒体质量与CD4⁺ T细胞数量为HAMD评分的独立负向预测因子。结论 CD4⁺/CD8⁺ T细胞数量及线粒体质量下降可能参与抑郁症发生，提示“线粒体功能障碍–T细胞失衡”可能是潜在病理机制。

关键词: 抑郁症, CD4⁺T细胞, CD8⁺T细胞, 线粒体质量, 免疫代谢, 生物标志物

Abstract: Objective To investigate the characteristics of changes in CD4⁺ and CD8⁺ T cell counts and mitochondrial mass(mean fluorescence intensity, MFI) in the peripheral blood of patients with depression, and to analyze their association with depression severity as assessed by the Hamilton Depression Rating Scale(HAMD) .Methods A total of 31 major depressive disorder (MDD) patients and 50 healthy controls were enrolled. Flow cytometry was used to assess T-cell subsets and mitochondrial quality. Welch’s t-tests and Mann-Whitney U tests were applied for group comparisons; Pearson correlation and FDR correction were used for association analyses. Multiple linear regression evaluated independent predictors of HAMD scores. Results CD4⁺ and CD8⁺ T-cell counts and MFI values were significantly reduced in MDD patients (P<0.01). CD8⁺T-cell MFI showed the strongest negative correlation with HAMD scores (R=－0.570, P<0.001). Regression analysis identified CD8⁺ MFI and CD4⁺ T-cell count as independent negative predictors of depression severity. Conclusion Reduced T-cell counts and mitochondrial quality are associated with depressive symptoms, suggesting that mitochondrial dysfunction and T-cell imbalance may contribute to MDD pathogenesis.

Key words: depression, CD4⁺T cells, CD8⁺ T cells, mitochondrial mass, immunometabolism, biomarkers

中图分类号:

R749

孙雪娇, 刘彦茹, 王志仁. CD4⁺和CD8⁺T细胞及线粒体质量与抑郁症的相关性[J]. 首都医科大学学报, 2025, 46(6): 1118-1125.

Sun Xuejiao , Liu Yanru , Wang Zhiren . Correlation between CD4⁺ and CD8⁺ T cells, mitochondrial mass, and depression[J]. Journal of Capital Medical University, 2025, 46(6): 1118-1125.

参考文献

［1］World Health Organization. Depression and other common mental disorders: global health estimates［R］. Geneva: World Health Organization, 2017.
［2］Bekkevold O J，Damås J K，Brumpton B M，et al. The causal role of C-reactive protein and interleukin-6 on anxiety and depression symptoms and life satisfaction：mendelian randomisation analyses in the HUNT study［J］. Psychol Med，2023，53(16)：7561－7568.
［3］Mendes-Silva A P，El-Ahmad P，Costa A P，et al. Decreased mitochondrial DNA integrity and elevated inflammatory markers in late-life depression：a longitudinal study［J］. Biol Psychiatry Glob Open Sci，2025，5(6)：100598.
［4］Gavril R，Dobrin P R，Pînzariu A C，et al. Predictive value of inflammatory biomarkers in assessing major depression in adults［J］. Biomedicines，2024，12(11)：2501.
［5］Beurel E，Toups M，Nemeroff C B. The bidirectional relationship of depression and inflammation：double trouble［J］. Neuron，2020，107(2)：234－256.
［6］Pattu V，Krause E，Chang H F，et al. IFNγ expression correlates with enhanced cytotoxicity in CD8⁺ T cells［J］. Int J Mol Sci，2025，26(14)：7024.
［7］Zhou D C，Yu H F，Yao H F，et al. A novel joint index based on peripheral blood CD4⁺/CD8⁺ T cell ratio，albumin level，and monocyte count to determine the severity of major depressive disorder［J］. BMC Psychiatry，2022，22(1)：248.
［8］Zhang W T，Wang C，Fu T T，et al. CD4 + T lymphocyte and cytokine profiles in depressive disorders［J］. BMC Psychiatry，2025，25(1)：911.
［9］Chen C，Zheng H，Horwitz E M，et al. Mitochondrial metabolic flexibility is critical for CD8⁺T cell antitumor immunity［J］. Sci Adv，2023，9(49)：eadf9522.
［10］Buck M D，O’Sullivan D，Klein Geltink R I，et al. Mitochondrial dynamics controls T cell fate through metabolic programming［J］. Cell，2016，166(1)：63－66.
［11］Ledderose C，Bao Y，Lidicky M，et al. Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling［J］. J Biol Chem，2014，289(37)：25936－25945.
［12］Bisle E，Haange S B，Rojas R，et al. Serum metabolomics in women with major depressive disorder：associations with mitochondrial function，inflammation，and oxidative stress［J］. Psychiatry Res，2025，351：116569.
［13］Bisle E，Haange S B，Rojas R，et al. Serum metabolomics in women with major depressive disorder：associations with mitochondrial function，inflammation，and oxidative stress［J］. Psychiatry Res，2025，351：116569.
［14］Hamilton M. A rating scale for depression［J］. J Neurol Neurosurg Psychiatry，1960，23(1)：56－62.
［15］Hamilton M. The assessment of anxiety states by rating［J］. Br J Med Psychol，1959，32(1)：50－55.
［16］Szałach Ł P，Cubała W J，Lisowska K A. Changes in T-cell subpopulations and cytokine levels in patients with treatment-resistant depression-a preliminary study［J］. Int J Mol Sci，2022，24(1)：479.
［17］Fan K Q，Li Y Y，Wang H L，et al. Stress-induced metabolic disorder in peripheral CD4⁺ T cells leads to anxiety-like behavior［J］. Cell，2019，179(4)：864－879. e19.
［18］Huang Y R，Chen Z N，Xu Y，et al. Mitochondrial mass and low mitochondrial membrane potential percentage of CD8⁺ T cell subsets are implicated with therapeutic effect in depressive disorder［J］. Front Psychiatry，2025，16：1550958.［PubMed］
［19］Poletti S，Zanardi R，Mandelli A，et al. Efficacy of low-dose interleukin 2 as add-on in the treatment of unipolar and bipolar depression［J］. Int J Neuropsychopharmacol，2025，28(Supplement_1)：i49.
［20］Moshfegh C M，Collins C W，Gunda V，et al. Mitochondrial superoxide disrupts the metabolic and epigenetic landscape of CD4⁺ and CD8⁺ T-lymphocytes［J］. Redox Biol，2019，27：101141.
［21］Setiawan E，Wilson A A，Mizrahi R，et al. Role of translocator protein density，a marker of neuroinflammation，in the brain during major depressive episodes［J］. JAMA Psychiatry，2015，72(3)：268－275.
［22］Tavenier J，Langkilde A，Haupt T H，et al. Immunosenescence of the CD8⁺ T cell compartment is associated with HIV-infection，but only weakly reflects age-related processes of adipose tissue，metabolism，and muscle in antiretroviral therapy-treated HIV-infected patients and controls［J］. BMC Immunol，2015，16：72.
［23］Tarasenko T N，Pacheco S E，Koenig M K，et al. Cytochrome c oxidase activity is a metabolic checkpoint that regulates cell fate decisions during T cell activation and differentiation［J］. Cell Metab，2017，25(6)：1254－1268. e7.
［24］Steinert E M，Furtado Bruza B，Danchine V D，et al. Mitochondrial respiration is necessary for CD8⁺ T cell proliferation and cell fate［J］. Nat Immunol，2025，26(8)：1267－1274.
［25］Xu T，Stewart K M，Wang X H，et al. Metabolic control of T(H)17 and induced T(reg) cell balance by an epigenetic mechanism［J］. Nature，2017，548(7666)：228－233.
［26］Keller J，Gomez R，Williams G，et al. HPA axis in major depression：Cortisol，clinical symptomatology and genetic variation predict cognition［J］. Mol Psychiatry，2017，22(4)：527－536.
［27］Watson K T，Simard J F，Henderson V W，et al. Association of insulin resistance with depression severity and remission status：defining a metabolic endophenotype of depression［J］. JAMA Psychiatry，2021，78(4)：439－441.
［28］Chen L P，Zeng X L，Zhou S J，et al. Correlation between serum high-sensitivity C-reactive protein，tumor necrosis factor-alpha，serum interleukin-6 and white matter integrity before and after the treatment of drug-Naïve patients with major depressive disorder［J］. Front Neurosci，2022，16：948637.
［29］Yu Y R，Imrichova H，Wang H P，et al. Disturbed mitochondrial dynamics in CD8⁺ TILs reinforce T cell exhaustion［J］. Nat Immunol，2020，21(12)：1540－1551.
［30］Wu H，Zhao X F，Hochrein S M，et al. Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming［J］. Nat Commun，2023，14(1)：6858.
［31］Alissafi T，Kalafati L，Lazari M，et al. Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity［J］. Cell Metab，2020，32(4)：591－604. e7.

［32］Maijo M，Ivory K，Clements S J，et al. One-year consumption of a Mediterranean-like dietary pattern with vitamin D3 supplements induced small scale but extensive changes of immune cell phenotype，co-receptor expression and innate immune responses in healthy elderly subjects：results from the United Kingdom arm of the NU-AGE trial［J］. Front Physiol，2018，9：997.

［33］Elhassan Y S，Kluckova K，Fletcher R S，et al. Nicotinamide riboside augments the aged human skeletal muscle NAD(+) metabolome and induces transcriptomic and anti-inflammatory signatures［J］. Cell Rep，2019，28(7)：1717－1728. e6.

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CD4⁺和CD8⁺T细胞及线粒体质量与抑郁症的相关性

Correlation between CD4⁺ and CD8⁺ T cells, mitochondrial mass, and depression

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CD4+和CD8+T细胞及线粒体质量与抑郁症的相关性

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CD4⁺和CD8⁺T细胞及线粒体质量与抑郁症的相关性

Correlation between CD4⁺ and CD8⁺ T cells, mitochondrial mass, and depression