T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder
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T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder. / Patas, Kostas; Willing, Anne; Demiralay, Cüneyt; Engler, Jan Broder; Lupu, Andreea; Ramien, Caren; Schäfer, Tobias; Gach, Christian; Stumm, Laura; Chan, Kenneth; Vignali, Marissa; Arck, Petra C; Friese, Manuel A; Pless, Ole; Wiedemann, Klaus; Agorastos, Agorastos; Gold, Stefan M.
In: FRONT IMMUNOL, Vol. 9, 2018, p. 291.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder
AU - Patas, Kostas
AU - Willing, Anne
AU - Demiralay, Cüneyt
AU - Engler, Jan Broder
AU - Lupu, Andreea
AU - Ramien, Caren
AU - Schäfer, Tobias
AU - Gach, Christian
AU - Stumm, Laura
AU - Chan, Kenneth
AU - Vignali, Marissa
AU - Arck, Petra C
AU - Friese, Manuel A
AU - Pless, Ole
AU - Wiedemann, Klaus
AU - Agorastos, Agorastos
AU - Gold, Stefan M
PY - 2018
Y1 - 2018
N2 - 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 Vβ 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.
AB - 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 Vβ 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.
KW - Journal Article
U2 - 10.3389/fimmu.2018.00291
DO - 10.3389/fimmu.2018.00291
M3 - SCORING: Journal article
C2 - 29515587
VL - 9
SP - 291
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -
