IL-7 Abrogates the Immunosuppressive Function of Human Double-Negative T Cells by Activating Akt/mTOR Signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Andrea AllgäuerSimon Völkl

Abstract

Recently, a novel subset of TCRαβ(+) CD4(-) CD8(-) double-negative (DN) T cells was described to suppress immune responses in both mice and humans. Moreover, in murine models, infusion and/or activation of DN T cells specifically suppressed alloreactive T cells and prevented the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. We demonstrated that human DN T cells, like their murine counterparts, are highly potent suppressor cells of both CD4(+) and CD8(+) T cell responses. After hematopoietic stem cell transplantation and other lymphopenic conditions, IL-7 plays an important role in the reconstitution, survival, and homeostasis of the T cell compartment. Because IL-7 was shown to interfere with T cell functionality, we asked whether IL-7 affects the functionality of human DN T cells. Intriguingly, IL-7 diminished the suppressive activity of DN T cells toward allogeneic CD4(+) effector T cells. Of interest, our studies revealed that IL-7 activates the Akt/mechanistic target of rapamycin (mTOR) pathway in human DN T cells. Importantly, selective inhibition of the protein kinases Akt or mTOR reversed the IL-7 effect, thereby restoring the functionality of DN T cells, whereas inhib...Continue Reading

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Citations

Mar 2, 2016·Journal of Crohn's & Colitis·Anna CarrascoFernando Fernández-Bañares
Jun 2, 2016·Journal of Translational Medicine·Giovanni StalloneGiuseppe Grandaliano
Dec 24, 2019·Seminars in Cancer Biology·Devesh TewariAnupam Bishayee
May 23, 2021·Journal of Autoimmunity·Lu YangDong Zhang

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