Glucocorticoids and the emerging importance of T cell subsets in steroid refractory diseases

Abstract

Glucocorticoids remain the first-line treatment for a range of autoimmune and allergic diseases. However, 30% of patients fail to achieve disease control at tolerable systemic doses and continue to have an increased immune response with poor clinical outcome. This steroid refractory (SR) phenotype has previously been attributed to enhanced expression of inactive glucocorticoid receptor isoforms and cytokine-mediated suppression of glucocorticoid (GC) signaling, in particular by interleukin-2. These mechanisms are discussed, with emphasis on recent evidence for the role of the CD4(+)CD25(int) and GC-induced T regulatory cell subsets in perpetrating SR disease.