Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells
Mindi R.Walker, … , Jane H. Buckner, Steven F. Ziegler
Mindi R.Walker, … , Jane H. Buckner, Steven F. Ziegler
Published November 1, 2003
Citation Information: J Clin Invest. 2003;112(9):1437-1443. https://doi.org/10.1172/JCI19441.
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Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells

Abstract

CD4+CD25+ regulatory T (TR) cells have been described in both humans and mice. In mice, TR are thymically derived, and lack of TR leads to organ-specific autoimmunity. Recently, the forkhead/winged helix transcription factor, FoxP3, has been shown to be important for the function of TR cells in mice. In this study, human TR cells were examined and, in results similar to those of studies done in mice, expression of FoxP3 was found exclusively in CD4+CD25+ T cells and correlated with the suppressive activity of these cells. In contrast to the mouse studies, activation of human CD4+CD25– T cells led to expression of FoxP3. Expression of FoxP3 in activated human CD4+CD25+ cells also correlated with suppression of proliferation by these cells in freshly isolated CD4+CD25– T cells from the same donor. This suppression was cell-contact dependent and cytokine independent. Thus, in humans, during activation of CD4+CD25– T cells in an immune response, two populations of cells may arise, effector CD4+CD25+ and regulatory CD4+CD25+ T cells, with expression of FoxP3 correlated with regulatory activity. These data also raise the possibility that a failure to generate peripheral TR cells properly may contribute to autoimmune disease and suggest a possible therapeutic role for FoxP3 in the treatment of such diseases.

Authors

Mindi R.Walker, Deborah J. Kasprowicz, Vivian H. Gersuk, Angéle Bènard, Megan Van Landeghen, Jane H. Buckner, Steven F. Ziegler

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CD4+CD25+ regulatory T cells can be induced by activation of human CD4+C...
CD4+CD25+ regulatory T cells can be induced by activation of human CD4+CD25– PBMCs. (a) Schematic for generation of regulatory cells from CD4+CD25– cells, including a typical FACS plot with percentages for activated CD4+CD25– cells before sorting. Cells were incubated on plate-bound Ab (Y) for 24 hours and then transferred to a new well without Ab for 9 days. (b) Dot plots showing CD4 versus CD25 staining on CD4+ PBL before and after sorting with CD25 MACS microbeads. (c) Percent of CD4+CD25+ cells over time when CD4+CD25– cells were stimulated with plate-bound anti-CD3/soluble anti-CD28 or media. (d) Proliferation and suppression of freshly isolated CD4+CD25– T cells by CD4+CD25+ cells, which were generated by activating CD4+CD25– PBMCs with plate-bound anti-CD3/soluble anti-CD28 for 3 or 10 days. (e) Western blot analysis of FoxP3 expression on day 3 or day 10 after activation of CD4+CD25– T cells. Control cells were 293T cells transfected with a human FoxP3 cDNA clone. These data are from one experiment and are representative of six separate experiments with a suppression range of 60–95%.