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Cited by 74Tryptophan and brain disordersTreatment of Major DepressionT-cell and B-cell Immunology

T Cell phenotype and T cell receptor repertoire in patients with major depressive disorder

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Patas, Kostas, Willing, Anne, Demiralay, Cüneyt, Engler, Jan Broder, Lupu, Andreea, Ramien, Caren, Schäfer, Tobias, Gach, Christian +9 more·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.00291PMC PMC5826233
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Abstract

While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case-control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities (n = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject (n = 20). T cell phenotype and repertoire were interrogated using a combination of flow cytometry, gene expression analysis, and next generation sequencing. T cells from MDD patients showed significantly lower surface expression of the chemokine receptors CXCR3 and CCR6, which are known to be central to T cell differentiation and trafficking. In addition, we observed a shift within the CD4+ T cell compartment characterized by a higher frequency of CD4+CD25highCD127low/− cells and higher FOXP3 mRNA expression in purified CD4+ T cells obtained from patients with MDD. Finally, flow cytometry-based TCR V repertoire analysis indicated a less diverse CD4+ T cell repertoire in MDD, which was corroborated by next generation sequencing of the TCR β chain CDR3 region. Overall, these results suggest that T cell phenotype and TCR utilization are skewed on several levels in patients with MDD. Our study identifies putative cellular and molecular signatures of dysregulated adaptive immunity and reinforces the notion that T cells are a pathophysiologically relevant cell population in this disorder.

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Authors
Patas, K., Willing, A., Demiralay, C., Engler, J. B., Lupu, A., Ramien, C., Schäfer, T., Gach, C., Stumm, L., Chan, K., Vignali, M., Arck, P. C., Friese, M. A., Pless, O., Wiedemann, K., Agorastos, A., & Gold, S. M.
Affiliations
  • University Medical Center Hamburg-Eppendorf (DE)
  • Fraunhofer Institute for Molecular Biology and Applied Ecology (DE)
  • Adaptive Biotechnologies (United States) (US)
  • Humboldt-Universität zu Berlin (DE)
Corresponding author
Gold, Stefan M.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-02-20
Volume
9
Pages
291-291
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.00291
PMC
PMC5826233
OpenAlex
W2790641239
Cited by
74
References
15
Citations by year
2026: 2 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 17 · 2021: 11 · 2020: 5 · 2019: 11 · 2018: 3
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
  • Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
Funders
  • European Commission (268381)
  • Bundesministerium für Bildung und Forschung (161A130, 16GW0082)
  • Deutsche Forschungsgemeinschaft (GO1357/8-1, GO1357/5-1, GO1357/5-2)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
major depressive disorder, T cell phenotype, T cell receptor repertoire, adaptive immunity, CXCR3, CCR6, CD4+ T cells, Foxp3, regulatory T cells, CDR3, inflammation, depression pathophysiology
MeSH terms
Adult, Cross-Sectional Studies, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Male, Middle Aged, Phenotype, Receptors, Antigen, T-Cell, T-Lymphocytes, Neuroimmunomodulation, Case-Control Studies, T-Lymphocyte Subsets

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