title: Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor.
abstract: We have previously shown that acute psychological stress alerts the adaptive immune response causing an increase in antigen-experienced effector T cells in the peripheral blood. T regulatory cells (Tregs) play a central role in maintaining self-tolerance and controlling autoimmune responses. Here, we analyzed for the first time the behaviour of Tregs in the context of a stress-induced activation of the adaptive immune response. 31 healthy young males underwent a brief laboratory stressor and, in a crossover design, served as their own unstressed controls. We quantified effects of acute stress on CD4(+)FOXP3(+) T regulatory cells and other T cell subpopulations using flow cytometry. In addition, the expression of Treg-related effector molecules and stress hormone receptors were analyzed in the subjects' peripheral T cells. We confirmed our previous observation of a stress-induced decrease in CD45RA(+)CCR7(+) "naïve" and CD45RA(-)CCR7+ "central memory" T cells while CD45RA(-)-CCR7(-) "memory effector" and CD45RA(+)CCR7(-) "terminally differentiated" effector T cells remained stable or increased. Importantly, we found acute psychological stress to cause a concomitant decrease in CD4(+)FOXP3(+) Tregs and in CD4(+) T cells expressing Treg-related effector molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and latency associated peptide (LAP). Finally, we observed beta(1)-adrenergic and glucorticoid alpha receptors to be overexpressed in Tregs, suggesting that these molecules might mediate stress-related effects on Tregs. In conclusion, inhibiting components of the adaptive immune response, like Tregs, are down-regulated during a stress-induced activation of the adaptive immune response. In situations of chronic stress, this scenario might result in an exacerbation of inflammatory conditions such as autoimmune diseases.
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, Charité Campus Benjamin Franklin, Free and Humboldt University, Berlin, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Freier
authors.forename: Cora Stefanie
authors.initials: CS
authors.lastname: Weber
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowottne
authors.forename: Christiane
authors.initials: C
authors.lastname: Horn
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.forename: Sabrina
authors.initials: S
authors.lastname: Meyer
authors.forename: York
authors.initials: Y
authors.lastname: Hildebrandt
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.forename: Yanran
authors.initials: Y
authors.lastname: Cao
authors.forename: Caroline
authors.initials: C
authors.lastname: Pabst
authors.forename: Julia
authors.initials: J
authors.lastname: Muzzulini
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schnee
authors.forename: Monika Christine
authors.initials: MC
authors.lastname: Brunner-Weinzierl
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marangolo
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Deter
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018342:Receptors, Adrenergic, beta-1; D011965:Receptors, Glucocorticoid; D053773:Transforming Growth Factor beta1; C411470:glucocorticoid receptor alpha