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RESEARCH PRODUCT

Infectious Tolerance

Michael StassenJiirgen KnopAlexander EnkHacer KakirmanHelmut JonuleitEdgar Schmitt

subject

TGF-βCD4-Positive T-Lymphocyteshuman regulatory T cellsT-LymphocytesImmunologyCellchemical and pharmacologic phenomenaIn Vitro TechniquesLymphocyte ActivationT-Lymphocytes RegulatoryImmune toleranceInterleukin 21AntigenTransforming Growth Factor betaCD4+CD25+ T cellsCell AdhesionImmune TolerancemedicineHumansImmunology and AllergyCytotoxic T cellIL-2 receptorbiologyBrief Definitive ReportModels ImmunologicalReceptors Interleukin-2hemic and immune systemsT-Lymphocytes Helper-InducerTransforming growth factor betainfectious tolerancemedicine.anatomical_structureT cell inhibitionImmunologyCancer researchbiology.proteinTransforming growth factor

description

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.

yearjournalcountryeditionlanguage
2002-07-15Journal of Experimental Medicine
https://doi.org/10.1084/jem.20020394