The characterization and role of regulatory T cells in immune reactions.

Regulatory T cells (Tregs) having CD4+ CD25+ Foxp3+ or CD4+ IL-10+ (Tr1) phenotype and capable of inducing anergy towards self- and alloantigens play an important role in autoimmunity, as well as in tolerance of allografts, pregnancy and cancer. Both thymus-derived T CD4+ CD25+ Foxp3+ natural cells and peripherally-induced T CD4+ CD25+ Foxp3+ cells prevent migration of effector immunocytes to target organs and inhibit their cooperation with antigen-presenting cells. The suppressive function of CD4+ CD25+ Foxp3+ Tregs depends on interactions between stimulatory (IL-2, CTLA-4) and inhibitory (GITR, CD28) signals, on stimulation of indoleamine 2,3-dioxygenase (IDO) activity in dendritic cells via CD80/CD86 molecules, and finally on cell-cell inhibition of effector cells by membrane-bound TGF-beta. Anergy of effector cells caused by Tregs could provoke them to secretion of IL-10/TGF-beta in mechanism of "bystander suppression". Tr1 cells constitute the distinctive Tregs population which originates from IL-10-primed naïve T cells or from T cells induced by tolerogenic IL-10/TGF-beta-expressing dendritic cells. The suppressive activity of Tr1 cells is based on local IL-10/TGF-beta secretion in the peripheral tissues. Tregs have a privileged place in the net of immunological interactions which makes them a possible common target for therapeutic interventions in different diseases.