Rôle des cytokines gamma(c)-dépendantes dans la différenciation, la mémoire et l'épuisement des lymphocytes T CD8

Chercheurs-boursiers cliniciens - Junior 1 | Concours 2012-2013


Hélène Decaluwe

Centre de recherche du CHU Ste-Justine

 

Domaine : Maladies infectieuses et immunitaires

Lymphocytes are the critical cells involved in the elimination of viruses or cancerous cells. Their differentiation into potent memory cells is the basis for vaccination in humans. Signals involved in their differentiation impact the potential for protective responses upon vaccination or after an infectious event. Some of these essential signals are delivered by cytokines present at the time of infection or immunization. The role of specific cytokines in the context of viral infections, such as influenza, HIV/AIDS or hepatitis C, remains poorly defined. Furthermore, their importance in the prevention of childhood leukemias is uncertain. This project will evaluate the impact of three cytokines, IL-2, IL-15 and IL-21, in the differentiation and function of CD8 memory T lymphocytes. Three distinct situations will be compared: differentiation after an acute viral infection, after a chronic viral infection or upon leukemia. By using unique mouse models, we will examine the expansion, proliferation and formation of memory T cells in the presence or absence of cytokines. The quality of the lymphocytes generated will be tested by evaluating their capacity to eliminate virally infected or cancerous cells. The cellular and molecular pathways modified by the presence or absence of the cytokines will also be analyzed. Together, these results will define the mechanisms by which cytokines influence functional memory generation. This will provide new critical information needed to promote potent immune responses during severe viral infections or cancer and to improve and design new therapeutic regimens for these diseases.