Le lundi 23 mai 2022, Madame Caroline RITACCO subira l'examen en vue de l'obtention du grade académique de Docteur en Sciences biomédicales et pharmaceutiques sous la direction de Monsieur Michel MOUTSCHEN

Cette épreuve consistera en la défense publique d'un mémoire intitulé :

"Contribution to the study of the homeostasis of regulatory T cells after allogeneic hematopoietic stem cell transplantation"

Allogeneic hematopoietic cell transplantation (allo-HCT) is the best treatment option for many patients suffering from hematological malignancies. This approach relies on immune-mediated graft-versus-tumor (GVT) effects for tumor eradication. Besides mediating GVT effects, donor T cells present in the graft can also cause graft versus-host-disease (GVHD), a life-threatening complication of allo-HCT. It is now well established that regulatory T cells (Treg) represent a heterogeneous group of CD4+ T cells that play a crucial role for GVHD prevention and attenuation. Treg constitutively express the high-affinity α-subunit within αβγ form of IL-2 receptor (CD25) and are mainly dependent on IL-2 secreted by activated T cells for their homeostasis. Previous studies have demonstrated that Treg homeostasis was altered in allo-HCT. In this thesis, in a first project, we assessed the ability of various Treg subsets to phosphorylate STAT5 in response to IL-2 or IL-7 stimulation in vitro and compared their frequencies in healthy controls and in allo-HCT patients with or without chronic GVHD. 

In a second project, we investigated the impact of the administration of post-transplant cyclophosphamide (PTCy) on xenogeneic GVHD and on GVT effects in humanized mouse models, with a special focus on its impact on Treg.

Le Jury sera composé de :

Michel Moutschen (Président), Christophe Desmet (Secrétaire), Frédéric Baron (Promoteur), Yves Beguin, José Cohen (Institut Mondor de recherche biomédicale - Université Paris Est , France), André Gothot, Nathalie Jacobs, Sophie Lucas (UCL)