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 nave 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.