PD-L1 regulates the development, maintenance, and function of induced regulatory T cells

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(-/-) ant...

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Vydané v:The Journal of experimental medicine Ročník 206; číslo 13; s. 3015
Hlavní autori: Francisco, Loise M, Salinas, Victor H, Brown, Keturah E, Vanguri, Vijay K, Freeman, Gordon J, Kuchroo, Vijay K, Sharpe, Arlene H
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 21.12.2009
Predmet:
Animals
B7-1 Antigen - physiology
B7-H1 Antigen
Carrier Proteins - physiology
Forkhead Transcription Factors - physiology
Leukocyte Common Antigens - analysis
Lung - pathology
Membrane Glycoproteins - physiology
Mice
Mice, Inbred C57BL
Peptides - physiology
Phosphotransferases (Alcohol Group Acceptor) - physiology
Programmed Cell Death 1 Ligand 2 Protein
Proto-Oncogene Proteins c-akt - physiology
Signal Transduction
T-Lymphocytes, Regulatory - physiology
TOR Serine-Threonine Kinases
Transforming Growth Factor beta - physiology
ISSN:1540-9538, 1540-9538
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20090847