title: Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation.
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.
authors.affiliation: Department of Psychiatry, University of Muenster, Germany; Radiology Morphological Solutions, Rotterdam, The Netherlands. Electronic address: laura.grosse@ukmuenster.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Grosse
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoogenboezem
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambrée
authors.affiliation: Department of Psychology, University of Duisburg-Essen, Germany.
authors.forename: Silja
authors.initials: S
authors.lastname: Bellingrath
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Jörgens
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: de Wit
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Annemarie M
authors.initials: AM
authors.lastname: Wijkhuijs
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003865:Major Depressive Disorder / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: Inflammation; Lymphocytes; Major depressive disorder; Monocyte gene expression; Natural killer cells; T helper cells; T regulatory cells