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 β1-adrenergic and glucorticoid α 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. © 2009 Elsevier Ltd.