Abnormalities in regulatory T cells and natural killer cells in major depressive disorder

Abstract Major depressive disorder (MDD) is associated with increased levels of acute phase proteins, pro-inflammatory cytokines, and monocytosis, indicative of immune activation. However, in apparent contrast to evidence of depression-associated inflammation, a reduction in natural killer cell (NKC) activity is also a well-replicated finding, leading to the hypothesis that MDD is an “immunosuppressive” disorder. Here used FACS analysis to identify key subtypes of T cells and NKC in 36 healthy controls (HC) and 34 physically healthy, unmedicated patients with MDD matched for age and body mass index. After controlling for group differences in gender, we found a greater percentage of monocytes and Treg cells (relative to total live cells) in the MDD group. In addition, there was a smaller percentage of putative regulatory NKC (CD56+CD16-) but not cytotoxic NKC (CD56+CD16+) or NK T-cells (NKT) in the MDD patients. In wild-type mice, a microglia-driven, T cell-dependent protective response has been shown to be restricted by Treg cells, raising the possibility that the elevation of Treg cells in the MDD group may impair the resolution of acute pathophysiological changes leading to chronic inflammation. The depression-associated reduction in putative regulatory NKC but not effector NKC favors the hypothesis that MDD is associated with inflammation rather than immunosuppression.