'Vive la Résistance!'--the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression.

Wohlfert EA; Clark RB

doi:10.1016/j.it.2007.02.003

'Vive la Résistance!'--the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression.

Wohlfert EA ¹,

Clark RB

Affiliations

1. Department of Immunology, University of Connecticut Health Center, Farmington, CT 06032, USA.
Authors
Wohlfert EA¹
(1 author)

Trends in Immunology, 27 Feb 2007, 28(4):154-160
https://doi.org/10.1016/j.it.2007.02.003 PMID: 17329168

Review

Abstract

CD4+CD25+ regulatory T (Treg) cells have emerged as important regulators of immune responses but the mechanisms through which Treg cells mediate suppression are still unclear. Recently, several studies have identified murine models of spontaneous autoimmunity or genetically engineered mice in which the Treg cells function normally but the CD4+CD25- T effector (Teff) cells are resistant to Treg-mediated suppression. Here, we postulate that the activation status of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway in Teff cells is a primary determinant of Teff cell sensitivity to Treg cell-mediated suppression, and that when the PI3K-Akt pathway is hyperactivated in Teff cells, these cells are resistant to Treg cell-mediated suppression. We further postulate that this paradigm can mechanistically link abnormalities in the PI3K-Akt pathway to the development of autoimmunity.

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Read article at publisher's site: https://doi.org/10.1016/j.it.2007.02.003

References

Articles referenced by this article (44)

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Search life-sciences literature (45,103,589 articles, preprints and more)

'Vive la Résistance!'--the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression.

Affiliations

Authors

Abstract

Full text links

References

From vanilla to 28 flavors: multiple varieties of T regulatory cells.

Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice.

NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells.

T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.

MRL/Mp CD4+,CD25- T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus.

Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells.

TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis.

Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells.

Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development.

Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo.

Citations & impact

Impact metrics

Citations of article over time

Article citations

Protein Phosphatase 2A: Role in T Cells and Diseases.

Boosting regulatory T cell function for the treatment of autoimmune diseases - That's only half the battle!

IL-6 and TNFα Drive Extensive Proliferation of Human Tregs Without Compromising Their Lineage Stability or Function.

Overproduction of IL-2 by Cbl-b deficient CD4⁺ T cells provides resistance against regulatory T cells.

Coupled feedback regulation of nuclear factor of activated T-cells (NFAT) modulates activation-induced cell death of T cells.

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'Vive la Résistance!'--the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression.

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