Human CD(4+)CD(25+) regulatory T cells and infectious tolerance.
Control of autoaggressive T cells by regulatory T cells (Treg) is essential to ensuring peripheral tolerance. Several subsets of CD(4+) T cells with suppressive properties have been described, including induced T helper (Th) type 3 and T regulatory (Tr) type 1 cells and naturally occurring CD(4+)CD(25+) Treg. CD(4+)CD(25+) Treg suppress the response of conventional T cells in a cell contact-dependent manner, whereas Th3 and Tr1 cells produce immunosuppressive cytokines. Two subsets of human CD(4+)CD(25+) Treg, characterized by expression of the integrins alpha4beta7 or alpha4beta1, are able to convey suppressive capacity to conventional CD(4+) T cells, thereby generating Th suppressor cells (Th(sup)). One outstanding feature is the generation of Th(sup) with distinct properties. alpha4beta7 Treg induce Tr1-like interleukin (IL)-10-producing Th(sup), whereas alpha4beta1 Treg induce Th3-like Th(sup), which produce transforming growth factor (TGF)-beta. Thus, our findings reconcile contradictory results clearly demonstrating that suppression is contact dependent in vitro but mediated by soluble factors (IL-10 and TGF-beta) in vivo.
Stassen
Michael
M
Institute of Immunology, Johannes Gutenberg-University, Mainz, Germany. michael.stassen@gmx.de.
Schmitt
Edgar
E
Jonuleit
Helmut
H
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D015375:Receptors, Interleukin-2