Allgäuer A, Schreiner E, Ferrazzi F, Ekici AB, Gerbitz A, Mackensen A, Voelkl S (2015)
Publication Type: Journal article
Publication year: 2015
Book Volume: 195
Pages Range: 3139-48
Journal Issue: 7
Recently, a novel subset of TCR??(+) 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 inhibition of other central T cell signaling pathways did not. Further analyses suggest that the IL-7/Akt/mTOR signaling cascade downregulates anergy-associated genes and upregulates activation- and proliferation-associated factors that may be crucial for DN T cell functionality. These findings indicate that IL-7 and Akt/mTOR signaling are critical factors for the suppressive capacity of DN T cells. Targeting of these pathways by pharmacological agents may restore and/or enhance DN T cell functionality in graft-versus-host disease.
APA:
Allgäuer, A., Schreiner, E., Ferrazzi, F., Ekici, A.B., Gerbitz, A., Mackensen, A., & Voelkl, S. (2015). IL-7 Abrogates the Immunosuppressive Function of Human Double-Negative T Cells by Activating Akt/mTOR Signaling. Journal of Immunology, 195(7), 3139-48. https://doi.org/10.4049/jimmunol.1501389
MLA:
Allgäuer, Andrea, et al. "IL-7 Abrogates the Immunosuppressive Function of Human Double-Negative T Cells by Activating Akt/mTOR Signaling." Journal of Immunology 195.7 (2015): 3139-48.
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