Glucocorticoid amplifies IL‐2‐dependent expansion of functional FoxP3+CD4+CD25+ T regulatory cells in vivo and enhances their capacity to suppress EAE

• Published in: European journal of immunology Vol. 36; no. 8; pp. 2139 - 2149
• Main Authors: Chen, Xin, Oppenheim, Joost J., Winkler‐Pickett, Robin T., Ortaldo, John R., Howard, O. M. Zack
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-08-2006
• Subjects: Animals; CD4+CD25+ T regulatory cells; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cell Proliferation - drug effects; Cells, Cultured; Dexamethasone; Dexamethasone - pharmacology; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - metabolism; Experimental autoimmune encephalomyelitis; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Glucocorticoids - pharmacology; IL‐2; Interleukin-2 - pharmacology; Mice; Receptors, Interleukin-2 - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200635873

IL‐2 is crucial for the production of CD4+CD25+ T regulatory (Treg) cells while important for the generation of effective T cell‐mediated immunity. How to exploit the capacity of IL‐2 to expand Treg cells, while restraining activation of T effector (Teff) cells, is an important and unanswered therapeutic question. Dexamethasone (Dex), a synthetic glucocorticoid steroid, has been reported to suppress IL‐2‐mediated activation of Teff cells and increase the proportion of Treg cells. Thus, we hypothesized that glucocorticoids may be useful as costimulants to amplify IL‐2‐mediated selective expansion of Treg cells. We show in this study that short‐term simultaneous administration of Dex and IL‐2 markedly expanded functional suppressive Foxp3+CD4+CD25+ T cells in murine peripheral lymphoid tissues. In a myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis (EAE) mouse model, we observed that splenic CD4+CD25+ T cells failed to suppress the proliferation of CD4+CD25– T cells. Pretreatment with Dex/IL‐2 remarkably increased the proportion of CD4+FoxP3+ cells and partially restored the function of splenic CD4+CD25+ T cells, and inhibited the development of EAE. Therefore, the combination of glucocorticoid and IL‐2, two currently used therapeutics, may provide a novel approach for the treatment of autoimmune diseases, transplant rejection and graft‐vs.‐host disease.