T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder

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 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.

Peripheral Blood Cell–Stratified Subgroups of Inflamed Depression

“…Blood proteins, such as cytokines and CRP, have been the focus of most immune biomarker research in psychiatry to SEE COMMENTARY ON date; the potential utility of cellular immune markers has been relatively underexplored (12)(13)(14)(15)(16)(17)(18). Most case-control studies of leukocyte subsets have used small samples and limited immunophenotyping panels and have generated inconsistent results.…”

“…Depression has been reproducibly associated with leukocytosis, increased neutrophil-to-lymphocyte ratio, and increased ratio of CD4 1 to CD8 1 T cells (19)(20)(21). However, there are less consistent results concerning regulatory T cells, T-helper 17 cells, natural killer (NK) cells, monocytes, and B cells (12)(13)(14)(15)(16)18,22). Other psychiatric disorders, including schizophrenia, bipolar disorder, and autism, have also been associated with altered cell counts (23)(24)(25).…”

The interplay between depression and tuberculosis

“…First, the differentiation and polarization of CD4 + T cells are altered among patients with major depression disorder, as different ratios of Th1, Th17, and Treg . Second, the receptors for neurotransmitter on T cells is altered and T cells cannot appropriately function in depressive patients . Third, the proinflammatory cytokines microenvironment somehow inhibit the function of T cells .…”

“…106,107 Second, the receptors for neurotransmitter on T cells is altered and T cells cannot appropriately function in depressive patients. 108 Third, the proinflammatory cytokines microenvironment somehow inhibit the function of T cells. 92 Therefore, in spite of the number of CD4 + T cells in depression may or may not decreased, the functions of CD4 + T cells might be suppressed due to reduction proliferative response of T cell and induction of T cell apoptosis.…”

Neuroimmune nexus of depression and dementia: Shared mechanisms and therapeutic targets

“…In the plasma of both AD and MDD patients, imbalances in the relative ratios are noted of T lymphocyte phenotypes. Patients with both disorders have exhibited a skew in both the number and differentiated state of plasma immunosuppressive T reg lymphocytes (Li et al, 2010;Lombardi, Garcia, Rey, & Cacabelos, 1999;Maes et al, 1992;Oberstein et al, 2018;Tan et al, 2002), as well as increased numbers of Th17 lymphocytes (Chen et al, 2011;Patas et al, 2018;Oberstein et al, 2018). As differentiated T reg lymphocytes are suggested to suppress Th17 differentiation (Chaudhry et al, 2009), impairment of this regulatory mechanism may in part contribute to increased Th17 activity in each disorder.…”