Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells.
Regulatory CD4(+)CD25(+) T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact-mediated suppression of conventional CD4(+) T cells by human CD25(+) Treg cells is fixation resistant, independent from membrane-bound TGF-beta but requires activation and protein synthesis of CD25(+) Treg cells. Coactivation of CD25(+) Treg cells with Treg cell-depleted CD4(+) T cells results in anergized CD4(+) T cells that in turn inhibit the activation of conventional, freshly isolated CD4(+) T helper (Th) cells. This infectious suppressive activity, transferred from CD25(+) Treg cells via cell contact, is cell contact-independent and partially mediated by soluble transforming growth factor (TGF)-beta. The induction of suppressive properties in conventional CD4(+) Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-beta in CD25(+) Treg cell-induced immunosuppression.
Jonuleit
Helmut
H
Department of Dermatology, University of Mainz, 55101 Mainz, Germany. jonuleit@hautklinik.klinik.uni-mainz.de
Schmitt
Edgar
E
Kakirman
Hacer
H
Stassen
Michael
M
Knop
Jürgen
J
Enk
Alexander H
AH
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D018448:Models, Immunological; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta