Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients

Abstract

Varicella zoster virus (VZV) infections cause varicella and subsequently herpes zoster upon reactivation. Immune-compromised individuals and the elderly are at high risk of developing herpes zoster due to waning of VZV-specific T-cell immunity. In the present study, a novel functional T-cell assay was developed to test the correlation between age and VZV-specific T-cell responses in peripheral blood from healthy individuals. Secondly, VZV-specific T-cell responses from renal transplant recipients were compared with healthy individuals. Monocytes were differentiated into mature monocyte-derived dendritic cells (moDCs) and were infected with VZV. T-cells were co-cultured with autologous moDCs infected with VZV and subjected to flowcytometric analysis to identify the phenotype (i.e., naïve [NA: CCR7(+) CD45RO(-) ], central [CM: CCR7(+) CD45RO(+) ] and effector memory [EM: CCR7(-) CD45RO(+) ] T-cells) and the frequency of VZV-reactive T-cell subsets by intra-cellular IFN-γ flowcytometry. In contrast to NA and CM T-cells, the frequency of VZV-reactive CD4 and CD8 EM T-cells was inversely correlated with age (P = 0.0007 and P = 0.01). No difference was found in the percentage of VZV-reactive CD4 NA, CM and EM T-cells between transplant recipients and controls. However, the percentage of VZV-reactive CD8 EM T-cells was significantly lower in transplant recipients compared to controls (P = 0.02). In conclusion, moDCs infected with VZV are efficient antigen presenting cells applicable to enumerate and characterize the phenotype and differentiation status of the systemic VZV-specific T-cell response ex-vivo. The data suggest that VZV-reactive EM T-cells are impaired in the elderly and renal transplant recipients.