Vol 43 (3) 2013, DOI: 10.1002/eji.201242613
Chronic exposure to stress predisposes to higher autoimmune susceptibility in C57BL/6mice: Glucocorticoids as a double-edged sword
Idan Harpaz, Shai Abutbul, Anna Nemirovsky, Ram Gal, Hagit Cohen, Alon Monsonego
Unfortunately, there are some errors in the results section “CVS decreases Treg frequency via an increase in the effector T-cell subsets” from the above-mentioned article. The corrected text is provided below.
CVS decreases Treg frequency via an increase in the effector T-cell subsets
Our data demonstrate an increase in pro-inflammatory cytokine levels induced by MOG35-55 immunization following CVS. However, it is yet not clear whether the CD4+CD25+ Treg population, which can strongly impact the progression of EAE, is affected by CVS. We initially found that the frequency of CD4+ T cells was decreased by 8% in the spleen and by 33.7% in circulating PBLs in stressed compared with non-stressed female mice (Supporting Information Fig. 3A and B).
The effect of CVS on the frequency of CD4+ Treg cells was examined by either intracellular staining of Foxp3 or surface staining of CD127 as a potential bio-marker of Treg cells ( and Supporting Information Fig. 3 and 4). FACS analysis revealed that within the CD4+CD25+ and CD4+CD25high subpopulations, the frequency of Foxp3+ T cells was significantly decreased following CVS (Fig. 7A–C). In addition, whereas stressed mice demonstrated a significant increase in the frequency of splenic CD4+CD25+ T cells as compared with non-stressed mice (17.3 and 14.7%, respectively, p < 0.05; Fig. 7D and E), the fraction of CD127− cells among CD4+CD25+T cells was significantly lower in stressed than in non-stressed mice in the spleen (76 and 82%, respectively, p < 0.05; Fig. 7D and E) and in the blood (65.6 and 77%, respectively, p < 0.01; Supporting Information Fig. 5A and B). Comparing the frequency of cells expressing CD127− and CD127+ within splenic (Fig. 7D and F) and blood-derived (Supporting Information Fig. 5A and C) CD4+T cells revealed a significant decrease in the CD127−/CD127+ ratio in stressed mice compared with non-stressed mice. This was evident primarily within the CD4+CD25high subpopulation and to a lesser extent within the CD25low population, but was not evident in the CD25− subpopulation. Notably, the frequency of CD25+CD127+, but not CD25+CD127−, within splenic (Fig. 7G) and blood-derived (Supporting Information Fig. 5D) CD4+ T cells was significantly higher in stressed than in non-stressed mice. This indicates that the increased Teff/Treg ratio in stressed mice resulted from an increase in the effector T-cell population with no change in the Treg-cell population.
The frequency of Foxp3+ cells and the CD127−/CD127+ ratio among CD4+CD25+ T cells were then examined following EAE induction. As shown in Figure 7H, whereas the frequency of splenic Foxp3 Treg cells among CD4+ T cells was generally reduced in stressed mice prior to EAE induction, no difference was observed between stressed and non-stressed mice following EAE. Similarly, no difference was observed in the CD127−/CD127+ ratio among blood-derived CD4+CD25+ T cells between stressed and non-stressed mice following EAE induction or remission (Supporting Information Fig. 5E). Notably, both the frequency of Foxp3+ cells (Fig. 7H) and the CD127−/CD127+ ratio among CD4+CD25+ T cells (Supporting Information Fig. 5E) were reduced at EAE onset and gradually recovered toward disease remission.