title: Antagonistic and synergistic effects of glucocorticoids and IL-7 on CD4+ T cell activation.
abstract: Glucocorticoids (GCs) are steroidal compounds widely used to treat chronic and acute inflammatory diseases. In particular, GCs at pharmacological doses induce apoptosis of activated and naïve T cells, inhibit their proliferation and block pro-inflammatory cytokine secretion. At physiological concentrations, the effect of these steroids on T cell immunity are not yet fully understood, and various studies reported paradoxical roles exerted by GCs on T cell immunity. Here, we show that GCs surprisingly induce proliferation of activated CD4(+) T cells in the presence of IL-7, a cytokine secreted in the thymus and at mucosal sites. Increased proliferation is dependent on a GC-mediated survival of mitotic cells. Moreover, we observe a downmodulation of Th1 cytokine secretion in cells treated with GCs, an outcome which is not affected by the presence of IL-7. GCs exert thus a positive role in the presence of IL-7 by enhancing proliferation of CD4(+) T cells and simultaneously a negative role by suppressing pro-inflammatory cytokine production.
authors.affiliation: Division of Immunopathology, Institute of Pathology, University of Bern, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Cima
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuhrer
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004336:Drug Antagonism; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005938:Glucocorticoids; D015851:Interleukin-7