CD4+CD25+ Regulatory T Cell Depletion Modulates Anxiety and Depression-Like Behaviors in Mice

Abstract

Stress has been shown to suppress immune function and increase susceptibility to inflammatory disease and psychiatric disease. CD4+CD25+ regulatory T (Treg) cells are prominent in immune regulation. This study was conducted to determine if anti-CD25 antibody (Ab) mediated depletion of Treg cells in mice susceptibility to stress-induced development of depression-like behaviors, as well as immunological and neurochemical activity. To accomplish this, an elevated plus-maze test (EPM), tail suspension test (TST), and forced swim test (FST) were used to examine depression-like behaviors upon chronic immobilization stress. Immune imbalance status was observed based on analysis of serum cytokines using a mouse cytometric bead array in conjunction with flow cytometry and changes in the levels of serotonin (5-HT) and dopamine (DA) in the brain were measured by high performance liquid chromatography (HPLC). The time spent in the open arms of the EPM decreased significantly and the immobility time in the FST increased significantly in the anti-CD25 Ab-treated group when compared with the non stressed wild-type group. In addition, interlukin-6 (IL-6), tumor necrosis factor-á (TNF-á), interlukin-2 (IL-2), interferon-gamma (IFN-γ), interlukin-4 (IL-4) and interlukin-17A (IL-17A) concentrations were significantly upregulated in the stressed anti-CD25 Ab-treated group when compared with the non stressed wild-type group. Furthermore, the non stressed anti-CD25 Ab-treated group displayed decreased 5-HT levels within the hippocampus when compared with the non stressed wild-type group. These results suggest that CD4+CD25+ Treg cell depletion modulated alterations in depressive behavior, cytokine and monoaminergic activity. Therefore, controlling CD4+CD25+ Treg cell function during stress may be a potent therapeutic strategy for the treatment of depression-like symptoms.

The Role of Interleukin-17A (IL-17A) in Depression

“…These results were confirmed by Chen et al who revealed that the number of Th17 cells, and the ratio of Th17/T regulatory cells and serum levels of IL-17A, were significantly increased in depressed patients compared to healthy controls (18). Upregulation of IL-17A in an animal model of depression has also been reported by Kim et al (25). Overall, according to the literature, it appears that Th17 cells and/or the expression of IL-17A are significantly associated with the pathogenesis of depression, and the parameters that decrease the expression of IL-17A can be considered potential candidates for adjuvant therapy of depression.…”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Moreover, decreases in counterregulatory immunologic functions including T regulatory cells (Tregs) and their production of the anti-inflammatory cytokines TGF-β and IL-10 have been described (Sutcigil et al, 2007;Li et al, 2010;Chen et al, 2011). Of note, depletion of Tregs leads to anxiety and depressive-like behavior in mice (Kim et al, 2012). Increases in the highly proinflammatory T helper type 17 (Th17) cells in conjunction with increased peripheral blood concentrations of IL-17 have also been found in patients with major depression .…”

Quercetin and Ellagic Acid in Gastric Ulcer Prevention: An Integrated Scheme of the Potential Mechanisms of Action From in Vivo Study

“…IL-2 release is controlled by CD4(+) CD25(+) regulatory T cells. In a chronic restraint stress mice model, the inhibition of CD4+ CD25+ regulatory T cells by anti-CD25 antibodies induced a significant increase in plasma IL-2 [83]. Moreover, IL-2 is also thought to potentiate H. pylori-associated gastroduodenal disorders by controlling Th1 immune responses [84].…”