Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients.
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.
Department of Internal Medicine-Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. n.vanbesouw@erasmusmc.nl
Nicole M
NM
van Besouw
Georges M G M
GM
Verjans
Joke M
JM
Zuijderwijk
Nicolle H R
NH
Litjens
Albert D M E
AD
Osterhaus
Willem
W
Weimar
D000328:Adult; D000367:Age Factors; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006562:Herpes Zoster / Q000276:immunology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7 / Q000276:immunology; D014775:Virus Activation
D000914:Antibodies, Viral; C515370:CCR7 protein, human; D054400:Receptors, CCR7; D007371:Interferon-gamma