CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis

Accumulating evidences support that CD4+CD25high T regulatory (Treg) cells play an essential role in controlling and preventing autoimmunity. Paradoxically, RA patients have elevated numbers of circulating CD4+CD25high T cells, however, the inflammation is still ongoing. Further identification of these CD4+CD25high T cells may contribute to a better understanding of underlying mechanisms. We show here that these CD4+CD25high T cells were composed of CD4+CD25highFoxP3+ Treg cells and activated CD4+CD25highFoxP3− effector cells. Moreover, there were significantly more Treg cells and effector T cells expressing GITR, and more monocytes expressing GITR-L. Thus, although RA patients have elevated numbers of CD4+CD25high T cells, the suppressive function is not increased, because of the increased number of activated effector T cells. In addition, the GITR-GITR-L system was activated in RA patients, which might lead to diminish suppressive activity of Treg cells and/or lead to resistance of activated effector T cells to suppression by Treg cells, thus, contributing to the ongoing inflammation in RA patients.