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

• Published in: Psychoneuroendocrinology 2010-06, Vol.35 (5), p.663-673
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 0306-4530
• DOI: 10.1016/j.psyneuen.2009.10.005

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 super(+)FOXP3 super(+) 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 super(+)CCR7 super(+) "naive" and CD45RA super(-)CCR7+ "central memory" T cells while CD45RA super(-)-CCR7 super(-) "memory effector" and CD45RA super(+)CCR7 super(-) "terminally differentiated" effector T cells remained stable or increased. Importantly, we found acute psychological stress to cause a concomitant decrease in CD4 super(+)FOXP3 super(+) Tregs and in CD4 super(+) T cells expressing Treg-related effector molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and latency associated peptide (LAP). Finally, we observed beta sub(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.