Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation

Brain Behav Immun. 2016 May:54:38-44. doi: 10.1016/j.bbi.2015.12.003. Epub 2015 Dec 8.

Abstract

Background: In a previous study, we found an up-regulated inflammatory monocyte gene expression profile in major depressive disorder (MDD) patients aged ⩾ 28 years and a down-regulated inflammatory gene expression profile in MDD patients aged<28 years. In the same sample of patients, we aimed to investigate immune dysregulation in the lymphocyte arm of the immune system, particularly in the context of the described monocyte (de-)activation states.

Methods: From deep frozen leukocytes, circulating percentages of monocytes, lymphocytes, B, T, and natural killer (NK) cells, and various functional subsets of T and T helper (Th) cells (Th1, Th2, Th17, and natural T regulatory cells) were measured in N=50 MDD patients and N=58 age- and gender-matched healthy controls (HC). In addition, serum levels of interleukin (IL)-6, sCD25, IL-7, IL-3, SCF, IGF-BP2, and EGF were evaluated.

Results: MDD patients were in general characterized by an impaired maturation of Th2 cells, Th17 cells, and NK cells and by decreased serum levels of IL-7 and sCD25. MDD patients aged ⩾ 28 years additionally exhibited decreased percentages of CD4(+)CD25(high)FoxP3(+) T regulatory cells, next to signs of the above described partial T cell defects. Natural T regulatory cells were inversely associated with the pro-inflammatory state of the monocytes (r=-.311; p=.034) that characterized this patient subgroup.

Conclusions: Deficiencies of the NK and T (regulatory) cell system and inflammatory monocyte immune activation co-occur as partly interrelated phenomena within the same MDD patients.

Keywords: Inflammation; Lymphocytes; Major depressive disorder; Monocyte gene expression; Natural killer cells; T helper cells; T regulatory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / metabolism
  • Depressive Disorder, Major / immunology*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / pathology
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Cytokines