Sylvain Latour

Lymphocyte activation and susceptibility to EBV

The efficiency and the homeostasis of adaptative immune responses are dependent of a variety of mechanisms that tightly regulated production, proliferation/death, functions of lymphocytes. During the immune response to a pathogen, lymphocytes are activated, proliferate and differentiate to acquire effector functions allowing the clearance of the pathogen, and finally die once the pathogen is eliminated. Numerous pathological conditions are caused by disequilibrium in these different processes. The team of Sylvain Latour studies these mechanisms and the physiopathology of conditions resulting from defects of these mechanisms during immune response to the Epstein Barr virus (EBV) infection. Several primary immunodeficiencies are associated with a defective immune response to EBV infection leading to lymphoproliferative and inflammatory disorders including lymphoma and  haemophagocytic lymphohistiocytosis. The team recently showed that CTPS1 (CTP Synthetase 1), an enzyme involved in the de novo synthesis of the nucleotide CTP, is a key factor required for the proliferation of activated lymphocytes. CTPS1 deficiency in humans resulted in a high susceptibility to viral infections in particular to EBV infection, highlightening the crucial role of proliferation and expansion of activated T lymphocytes during immune responses.

At present, the research project of the team evolves following three major directions:

1. identification and characterization of novel molecular defects associated with an abnormal immune response to EBV in patients with unknown genetic diagnosis;
2. biochemical, molecular and cellular analysis and characterization of activation and regulation pathways involved in the immune response to EBV, with a particular focus on genes/pathways involved in replication/ proliferation processes in activated T lymphocytes;
3. development of transgenic and KO mice models to study the mechanisms/gene functions underlying the physiopathology of these conditions.

Our "Study of genetic susceptibilities in pediatric lymphomas" ("Etude des susceptibilités génétiques dans les lymphomes pédiatriques ») is financially supported by the "Fédération Enfants et Santé".