Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment

Abstract

Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

“…recently, a study of CMV-specific T-cell subpopulations in renal transplant recipients demonstrated that low pretransplant CD8+ T-cells, low post-transplant day (PTD) 15 CD4+ or CD8+ T-cells, and low PTD60 and PTD180 CD4+ T-cells were predictive of subsequent CMV events [36]. Given the complex interactions between subpopulations of the cellular immune system, it is likely that both CMV-specific CD4+ and CD8+ T-cells play a role in the immune response to CMV infection [30].…”

“…Importantly, there is also evidence that CD4+ T cells have direct antiviral properties against CMV and play an essential role in abrogating reactivation and controlling primary CMV infection [38][39][40]. Given the importance of both CD4+ [4,30,34,36,41,42] and CD8+ [35,41,42] T-cells in the immune response to CMV, and the variety of clinical scenarios in which CMI assays may be used, detailed information regarding both CD4+ and CD8+ specific responses could be of clinical utility.…”

Monitoring of CMV-specific cell-mediated immunity with a commercial ELISA-based interferon-γ release assay in kidney transplant recipients treated with antithymocyte globulin

“…We and others have previously demonstrated that CMV-specific CD4 + T cells seem to play a more relevant role in the long-term viral control than the CD8 + subset. 2,26 Because the pool of viral peptides contained within the "CMV tube" mainly examines the response deployed by CMV-specific CD8 + T cells, 2,3 it may be speculated that the ability of the assay to properly identify patients lacking effective immune protection would decrease with time since transplantation. Therefore, we also explored a notably higher cutoff value (IFN-γ ≥ 7.0 IU/mL), which allowed us to identify KT recipients-accounting for a quarter of the overall cohort-in which the presence of protective CMV-CMI may be reliably predicted with a probability of over 75%.…”

Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay

“…Importantly, this approach still did not identify any obvious differences in the immune responses of these patients to provide an explanation for why some recipients had resolution of viraemia, and others recurrent viraemia despite a broad T cell response. We considered delayed immune reconstitution and immune suppression as factors in the occurrence and recurrence of viraemia, as HCMV-specific CMI is known to reconstitute more quickly in R+ than R-transplant recipients (Eid et al, 2010) and to reconstitute at different rates in different patients (Abate et al, 2010). However, that does not seem to explain the differences between patients who did and did not control viraemia, as all patients mounted T cell responses similar in magnitude and breadth to those seen in healthy seropositive donors.…”