AbstractsBiology & Animal Science

Despite the outstanding progress made in the understanding of the immune response against viral pathogens as well as on the care-management of transplant patients since the beginning of organ transplantation, hCMV infection still represents a major adverse complication among solid organ and hematopoietic cell transplant patients directly threatening both allograft and patient survival. While the advent of new and more potent anti-viral therapies used either as anti-viral treatments during active infection or as part of a preventive strategy, has lead to a significant reduction of the incidence of hCMV infection and its related complications, the occurrence of viral infection after transplantation is still considered as a rather unpredictable event. Certainly, this is the reflection of the considerably poor clinical monitoring of the viral immune susceptibility of each individual, which is merely based on the serological immune status combination between recipient and donor IgGantibody levels in sera and the direct assessment of the virus itself replicating in peripheral blood. The work constituting this doctoral thesis, researches further into how assessing hCMV-specific memory T and B-cell subsets, using a highly sensitive technique such as the ELiSPOT assay, which allows an accurate enumeration of antigen-specific immune responses at the single cell level, may help to better identify cellular and humoral immunized patients against the hCMV and thus, ultimately helping identifying kidney allograft recipients at high risk of hCMV infection after kidney transplantation. Importantly, an accurate and reliable knowledge of the immune-protection level against hCMV of transplant patients would allow individualization for anti-viral decision-making, thus personalizing this therapy. To date, an important body of evidence has been generated within the transplant scientific community, demonstrating the key role of the adaptive immunity, and particularly the cellular immune response in preventing, controlling and restricting viral replication. In contrast to previous reported data, in which have analyzed different types of organ transplant patients, receiving distinct type of anti-viral therapies and have fundamentally focused on the post-transplant setting, we here focused for the first time on the evaluation of hCMV-specific memory T and B cells against different immunogenic hCMV antigens prior to kidney transplantation in very clean and homogenous cohorts of kidney transplant recipients. In the first part of this thesis, it is shown that high frequencies of hCMV-specific T-cell responses, particularly against the IE-1 dominant hCMV antigen, may significantly improve the current serological identification of those kidney allograft recipients at high-risk for hCMV infection. Importantly, this approach was capable to discriminate such patients before transplantation with high sensitivity, regardless the type of preventive anti-viral strategy used based on the classical risk factors for the estimation of CMV risk after…