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.
Wilczynski
Jacek R
JR
Department of Gynecological Surgery, Polish Mother's Health Center Research Institute, Lodz, Poland. jrwil@post.pl
Radwan
Michal
M
Kalinka
Jaroslaw
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008954:Models, Biological; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10