International Immunology Advance Access originally published online on February 7, 2007
International Immunology 2007 19(3):227-237; doi:10.1093/intimm/dxl139
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood
Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
Correspondence to: B. Agrawal; E-mail: bagrawal{at}ualberta.ca.
The factors that influence the functionality of human CD4+CD25+ regulatory T cells are not well understood. We sought to characterize the effects of dendritic cells (DCs) on the in vitro regulatory activity of CD4+CD25+ T cells obtained from peripheral blood of healthy human donors. Flow cytometry showed that a higher proportion of CD4+CD25+(High) T cells expressed surface glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) and CTL-associated antigen 4 than CD4+CD25– or CD4+CD25+(Med–low) T cells. Intracellular Foxp3 was equivalently expressed on CD4+CD25+(All), CD4+CD25+(High), CD4+CD25+(Med–low) and CD4+CD25– T cell populations, irrespective of GITR and CTL-associated antigen 4 expression. CD4+CD25+ T cells were isolated and then cultured in vitro with CD4+CD25– responder T cells and stimulated with anti-CD3 antibodies, and immature dendritic cells (iDCs), mature dendritic cells (mDCs), PBMCs or PBMCs plus anti-CD28 antibodies to provide co-stimulation. In addition, secretion of the Th1 cytokine IFN-
, IL-2 and the immunoregulatory cytokines, IL-10 and transforming growth factor (TGF)-ß, were also assessed in these cultures. We found that iDCs and mDCs were capable of reversing the suppression of proliferation mediated by CD4+CD25+ regulatory T cells. However, the reversal of suppression by DCs was not dependent upon the increase of IFN- and IL-2 production or inhibition of IL-10 and/or TGF-ß production. Therefore, DCs are able to reverse the suppressive effect of regulatory T cells independent of cytokine production. These results suggest for the first time that human DCs possess unique abilities which allow them to influence the functions of regulatory T cells in order to provide fine-tuning in the regulation of T cell responses.
Keywords: CD4+25+ T cells, dendritic cells, human T cells, regulatory T cells
* These authors contributed equally to this work.
Received 25 September 2006, accepted 30 November 2006.