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