Cytomegalovirus-specific T-cell immunity to assign the infection status in individuals with passive immunity: A proof of principle

Abstract

BackgroundSerological analysis of the infection status with the human cytomegalovirus (CMV) may be inaccurate after transfusion of blood products due to the variable content of CMV-specific antibodies. ObjectivesIn this situation, analysis of cellular immunity may represent a more accurate parameter to assign the individual CMV-infection status. This hypothesis was assessed in a sequence of clinically defined events where a CMV-seronegative patient received human immunoglobulins before AB0 incompatible transplantation of a graft from his CMV-seropositive mother and developed CMV-primary infection thereafter. Study designHumoral immunity was analyzed using ELISA, and CMV-specific CD4 T-cells were flow-cytometrically quantified using intracellular cytokine staining after a 6h-stimulation with a CMV-antigen lysate. ResultsPrior to transplantation, both CMV-specific antibody-titers and T-cell frequencies were below detection limit. After plasma infusion, the patient was temporarily seropositive but remained T-cell negative indicating passive immunity. CMV-specific T-cells became stably detectable after graft-related primary infection, thereby confirming a truly positive infection status. ConclusionThis case provides an instructive proof of principle to show that CMV-specific CD4 T-cells may serve as an accurate marker to define the true CMV-infection status in situations where serological testing is limited by the presence of passively administered antibodies.