Submitted February 19, 2008
Accepted July 4, 2008
Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors
Hassen Kared, Bertrand Leforban, Ruddy Montandon, Amedee Renand, Esther Layseca Espinosa, Lucienne Chatenoud, Yvonne Rosenstein, Elke Schneider, Michel Dy, and Flora Zavala*
CNRS UMR 8147, Universite Paris Descartes, Faculte de Medecine, Paris, France
INSERM U580, Universite Paris Descartes, Faculte de Medecine, Paris, France
Instituto de Biotecnologia, Universidad Autonoma de Mexico, Cuernavaca, Morelos, Mexico
* Corresponding author; email: zavala{at}necker.fr.
Mechanisms of protection against autoimmune diseases by transplantation of autologous hematopoietic progenitors remain poorly defined. We recently demonstrated that, unlike medullary stem cells (HSCs), mobilized hematopoietic progenitors (HPCs) stimulate peripheral Foxp3+ regulatory T cell (Treg) expansion through cell-contact activation of Notch signalling and through as yet undetermined soluble factor(s), distinct from TGF-
1. Herein we identified one such soluble factor as GM-CSF, which is produced at higher levels by HPCs than HSCs and whose neutralization significantly reduces the growth-promoting effect of HPCs on Treg. Treg express a functional GM-CSF receptor 
-chain CD116 and proliferate in response to this cytokine independently from IL-2. GM-CSF-expanded Treg -like HPC-expanded Treg - display enhanced suppressive capacity relative to control Treg. Hence, mobilized progenitors stimulate Treg expansion both by cell-contact dependent mechanisms and by their production of GM-CSF.
