Submitted September 25, 2008
Accepted November 24, 2008
Naturally occurring regulatory T cells show reduced sensitivity towards oxidative stress induced cell death
Dimitrios Mougiakakos, C. Christian Johansson, and Rolf Kiessling*
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
* Corresponding author; email: rolf.kiessling{at}ki.se.
While several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor associated macrophages and myeloid derived suppressor cells. Oxidative stress is known to have detrimental effects on NK- and T cells during chronic inflammatory conditions and cancer. Paradoxically, higher numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA+, exhibit reduced sensitivity to oxidative stress-induced cell death and maintain their suppressive function, a phenomenon that may be due to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress.
