Improving our understanding of CMV-specific immune dysfunctionality in the context of immunosuppression

WP Objectives

To obtain insight into the underlying mechanisms/pathways of dysfunction and identify clear signatures of dysfunctionality at day 0 of transplantation and at day 0 of infection by:

• Describing in parallel all the actors of CMV specific immunity: humoral immunity, and T cells, NK cells and cytokines at day 0 and longitudinally after transplantation in order to confirm if a dysfunctional profile is associated to the risk of CMV replication post transplantation in R+ patients.

• Deciphering phenotype and molecular pathway involved in the dysfunction of NK and T cells in R+ patients through in vitro and in vivo models.

• Analysing viral kinetics and genome in parallel to the immune response to see if specific evasins of CMV or any other mutation that could impact viral fitness expressed in correlation to the lack of immune response, and if CMV proteomics in the biopsy of R+D+ patients is linked to increased risk of CMV replication after transplantation

• Defining a signature at day 0 or at early time of transplantation combining clinical immunological, virological and donor characteristics associated with the risk of developing CMV replication after transplantation in R+ patients