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. © 2012 Kim et al.

Indexed keywords

EMTREE drug terms: basiliximab; cytokine; dopamine; gamma interferon; interleukin 17; interleukin 2; interleukin 4; interleukin 6; serotonin; tumor necrosis factor alpha; CD4 antigen; dopamine; interleukin 2 receptor alpha; serotonin

EMTREE medical terms: animal cell; animal experiment; animal model; anxiety; article; brain level; CD4+ CD25+ T lymphocyte; controlled study; depression; flow cytometry; high performance liquid chromatography; hippocampus; immobilization stress; immune deficiency; lymphocyte depletion; monoaminergic system; nonhuman; protein blood level; regulatory T lymphocyte; upregulation; animal; animal behavior; blood; brain; C57BL mouse; immunology; metabolism; mouse

Species Index: Mus

MeSH: Animals; Antigens, CD4; Anxiety; Behavior, Animal; Brain; Chromatography, High Pressure Liquid; Cytokines; Depression; Dopamine; Flow Cytometry; Interleukin-2 Receptor alpha Subunit; Lymphocyte Depletion; Mice; Mice, Inbred C57BL; Serotonin; T-Lymphocytes, Regulatory
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: dopamine, 51-61-6, 62-31-7; gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; serotonin, 50-67-9;Antigens, CD4; Cytokines; Interleukin-2 Receptor alpha Subunit; Serotonin, 50-67-9