Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death

Eur J Immunol. 2004 Mar;34(3):859-869. doi: 10.1002/eji.200324506.


To evaluate the in vivo effect of immunosuppressive glucocorticoids on CD4+CD25+ T regulatory cells, we injected dexamethasone (Dex) into BALB/c mice. Administration of Dex enhanced the proportion of CD4+CD25+ cells and the ratio of CD4+CD25+ cells to CD4+CD25- cells in the lymphoid organs, especially in the thymus. This correlates with our in vitro observation that CD4+CD25+ T cells express higher levels of glucocorticoid receptor and Bcl-2, and are therefore more resistant to Dex-mediated cell death than CD4+CD25- T cells. Furthermore, IL-2 selectively protected CD4+CD25+ T cells from Dex-induced cell death, while IL-7 and IL-15 did not exert preferential protective effects. Dex-treated CD4+CD25+ T cells expressed higher levels of intracellular CTLA-4 and surface glucocorticoid-induced TNF receptor than fresh CD4+CD25+ T cells, but still failed to respond to TCR stimulation and inhibited proliferation of CD4+CD25- T cells. These results suggest that, in addition to suppressing cytokine transcription, Dex treatment is permissive for the survival of functional CD4+CD25+ T regulatory cells, and this property may contribute to the anti-inflammatory and immunosuppressive efficacy of glucocorticoids. Our data also suggest that selective protection of CD4+CD25+ T cell from apoptosis may constitute a role in immune tolerance for IL-2.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism
  • Apoptosis* / drug effects
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Dexamethasone / pharmacology*
  • Female
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids / pharmacology*
  • Interleukin-10 / metabolism
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Interleukin-2 / analysis*
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids
  • Interleukin-2
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Glucocorticoid
  • Receptors, Interleukin-2
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf18 protein, mouse
  • Interleukin-10
  • Dexamethasone