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Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood.
Int Immunol. 2007 Mar; 19(3):227-37.II

Abstract

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 T(h)1 cytokine IFN-gamma, IL-2 and the immunoregulatory cytokines, IL-10 and transforming growth factor (TGF)-beta, 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-gamma and IL-2 production or inhibition of IL-10 and/or TGF-beta 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.

Authors+Show Affiliations

Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17289657

Citation

Ahn, Justin S., et al. "Dendritic Cells Partially Abrogate the Regulatory Activity of CD4+CD25+ T Cells Present in the Human Peripheral Blood." International Immunology, vol. 19, no. 3, 2007, pp. 227-37.
Ahn JS, Krishnadas DK, Agrawal B. Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood. Int Immunol. 2007;19(3):227-37.
Ahn, J. S., Krishnadas, D. K., & Agrawal, B. (2007). Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood. International Immunology, 19(3), 227-37.
Ahn JS, Krishnadas DK, Agrawal B. Dendritic Cells Partially Abrogate the Regulatory Activity of CD4+CD25+ T Cells Present in the Human Peripheral Blood. Int Immunol. 2007;19(3):227-37. PubMed PMID: 17289657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood. AU - Ahn,Justin S, AU - Krishnadas,Deepa K, AU - Agrawal,Babita, Y1 - 2007/02/07/ PY - 2007/2/10/pubmed PY - 2007/5/5/medline PY - 2007/2/10/entrez SP - 227 EP - 37 JF - International immunology JO - Int Immunol VL - 19 IS - 3 N2 - 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 T(h)1 cytokine IFN-gamma, IL-2 and the immunoregulatory cytokines, IL-10 and transforming growth factor (TGF)-beta, 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-gamma and IL-2 production or inhibition of IL-10 and/or TGF-beta 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. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/17289657/Dendritic_cells_partially_abrogate_the_regulatory_activity_of_CD4+CD25+_T_cells_present_in_the_human_peripheral_blood_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxl139 DB - PRIME DP - Unbound Medicine ER -