Infectious Tolerance

By H. Jonuleit, E. Schmitt, H. Kakirman, M. Stassen, J. Knop, Alexander Enk. Journal of Experimental Medicine, 2002

668 citations recorded by the source corpus.

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-β 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)-β. 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-β in CD25+ Treg cell–induced immunosuppression.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/cc3089826ad89b0fde160b45826828fbd1d7d07b

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Citations in the corpus

Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. (2007, background): “Alternatively, co-culture with nTregs could amplify the levels of FOXP3 in suppressed cells as a mechanism of infectious tolerance (30, 31 ).”
Mechanisms of suppression by suppressor T cells (2005, background): “Alternatively, some CD4 + CD25 − cells may be induced by CD4 + CD25 + T cells to secrete TGF-β and/or IL-10 as proposed in some models of 'infectious tolerance”
The Foxp3+ regulatory T cell: a jack of all trades, master of regulation (2008, background): “For example, CD4 + T eff cells differentiate into IL-10- or TGF-β-producing adaptive T reg cells in the presence of T reg cells in vitro and in vivo , an observation more consistent with the idea of bystander suppression and infectious toleranc”
Tumor antigen-specific T helper cells in cancer immunity and immunotherapy (2005, result): “Recent studies have shown the induction of Th-like regulatory T cells by co-culture with natural T regulatory cells [28].”
Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-101 (2004, background): “Physical interaction between the CD4 CD25 inducer and CD4 CD25 cells was also required for their differentiation to suppressor cells (12, 13).”
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice (2007, background): “Finally, the presence of T reg cells early in life may facilitate the differentiation of T cells having suppressive properties but lacking Foxp3 expressio”
Molecular Mechanisms of Treg-Mediated T Cell Suppression (2012, background): “Suppressive cells generated by infectious tolerance use a mechanism involving TGF-β (Jonuleit et al., 2002).”
Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. (2004, result): “In in vivo following interaction with naturally occurring CD4 CD25 T cells as previously described in vitromany respects they resemble the Tr1 clones described by Roncarolo et al. in that they secrete both IFN- and (Dieckmann et al., 2002; Jonuleit et al., 2002).”
Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells1 (2004, background): “To explain the in vivo suppressive activity of Treg at low CD4 CD25:CD4 CD25 ratio while needing direct cell contact, several groups (53–56) have shown that CD4 CD25 Treg may convey a suppressive activity to other CD4 T cells that was found to be contact independent and either IL-10 (55) or TGF- dep”
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3 (2003, background): “Although not unanimous, increasing evidence has demonstrated that Treg produce/express higher levels of TGF-� , which plays a significant role in immune regulation in vitro and in vivo (27, 29, 30, 36 , 37).”
Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. (2005, result): “However, other studies have shown that IL-10 and transforming growth factor-h are responsible for the suppressive effect of regulatory T cells ( 41 , 42).”
Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy (2004, methodology): “It has been speculated previously that the spreading of suppression from CD4� CD25� T cells to responder T cells is an important mechanism by which regulatory T cells exert their effect in the maintenance of peripheral tolerance ( 19 ).”