Improving our understanding of CMV-specific immune response in a naïve individual in the context of immunosuppression

WP Objectives

To obtain insight into the events occurring before CMV-infection and into the very early mechanisms/pathways leading to CMV control in naïve immunocompromised patients, which can be related to either the absence of CMV transmissionfrom the graft and/or of a fast/efficient anti-CMV immune response. Altogether, this will lead us to identify clear signatures in CMV-naïve individuals at day 0 of transplantation associated with CMV control and at day 0 of infection associated with an efficient CMV control. Four objectives are defined:

1. To analyze in parallel all the actors of CMV-specific immunity: humoral immunity, αβ and γδ T cells, NK cells and cytokines at day 0 and longitudinally in order to decipher the characteristics of the immune actors associated to the risk of CMV replication post- transplantation in D+R- patients.

2. To decipher the molecular pathways involved in the early step of activation of NK and T cells in D+R- patients through in vitro and in vivo models.

3. To analyse viral kinetics and genome in parallel to the immune response to identify whether specific evasion molecules of CMV are expressed in correlation to the lack of immune response and if specific CMV proteomics and human donor microenvironment in the biopsy of R-D+ patients is linked to increased risk of CMV replication after transplantation

4. To define a signature at early time of transplantation combining clinical, immunological, virological and donor characteristics associated with the risk of developing CMV replication after transplantation in D+R- patients.