PD-L1 Regulates the Development, Maintenance, and Function of Induced Regulatory T Cells

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PD-L1 Regulates the Development, Maintenance, and Function of Induced Regulatory T Cells

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Title: PD-L1 Regulates the Development, Maintenance, and Function of Induced Regulatory T Cells
Author: Salinas, Victor H.; Vanguri, Vijay K.; Francisco, Loise Marie; Brown, Keturah Elise; Freeman, Gordon James; Kuchroo, Vijay Kumar; Sharpe, Arlene Helen

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Citation: Francisco, Loise M., Victor H. Salinas, Keturah E. Brown, Vijay K. Vanguri, Gordon J. Freeman, Vijay K. Kuchroo, and Arlene H. Sharpe. 2009. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. The Journal of Experimental Medicine 206(13): 3015-3029.
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Abstract: Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1\(^{−/−}\) antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1–coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1\(^{−/−}\) PD-L2\(^{−/−}\) Rag\(^{−/−}\) recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity.
Published Version: doi://10.1084/jem.20090847
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806460/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10169553
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