Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor

作者：Freier Eva; Weber Cora Stefanie; Nowottne Ulrike; Horn Christiane; Bartels Katrin; Meyer Sabrina; Hildebrandt York; Luetkens Tim; Cao Yanran; Pabst Caroline; Muzzulini Julia; Schnee Benjamin; Brunner Weinzierl Monika Christine; Marangolo Maurizio; Bokemeyer Carsten; Deter Hans Christian; Atanackovic Djordje^*

来源：Psychoneuroendocrinology, 2010, 35(5): 663-673.

DOI：10.1016/j.psyneuen.2009.10.005

• T cells
• T regulatory cells
• Cell surface molecules
• Acute psychological stress
• Psychoneuroimmunology
• Autoimmunity

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(+) "naive" 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 a 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.

• 出版日期2010-6