Immune Homeostasis Requires Several Biologic Factors Including Glucocorticoid Hormones

Abstract

Immunological tolerance can be achieved by several mechanisms including suppressor cells, soluble factors, and neurohormonal mediators. On the cellular level, we isolated a population of CD8+CD28- T cells capable of inhibiting anti-CD3 mAb-induced proliferation of autologous peripheral blood mononuclear cells in an HLA-I nonrestricted manner via production of IFN-gamma and IL-6. Interestingly, CD8+CD28- T cells from systemic lupus erythematosus patients with active disease do not display this inhibitory activity and show a marked imbalance between inhibitory (IL-6) and stimulatory (IL-12) cytokines. For soluble factors, we studied soluble HLA molecules (sHLAs) and double-stranded DNA (ds-DNA). Soluble HLA-I (sHLA-I) molecules induce soluble Fas ligand (sFasL) secretion and trigger apoptosis in phytohemagglutin (PHA)-activated Fas+ T cells. Double-stranded DNA binds to HLA-II molecules and inhibits HLA-II-mediated antigen presentation. On the neurohormonal side, we focused our attention on the immunological activity of corticosteroids (CTSs). CTSs inhibit recirculation of CD4+ T cells, suppress the proliferation and immunological function of activated T cells, and induce apoptosis of activated lymphocytes. Taken together, these data suggest the presence of a complex network of immunoregulatory mechanisms in which CTSs play a strong role supporting their recognized efficacy in the treatment of inflammatory and immunological diseases.