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

• Published in: Journal of medical virology Vol. 84; no. 12; pp. 2018 - 2025
• Main Authors: van Besouw, Nicole M., Verjans, Georges M.G.M., Zuijderwijk, Joke M., Litjens, Nicolle H.R., Osterhaus, Albert D.M.E., Weimar, Willem
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Adult; Age; Age Factors; Aged; Antibodies, Viral - analysis; Antibodies, Viral - immunology; Biological and medical sciences; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation; Coculture Techniques; Dendritic Cells - immunology; Dendritic Cells - virology; effector cells; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Geriatrics; Herpes Zoster - immunology; Herpes Zoster - virology; Herpesvirus 3, Human - immunology; Herpesvirus 3, Human - pathogenicity; Human viral diseases; Humans; IFN-γ; Immunity, Cellular; Immunologic Memory - immunology; Infectious diseases; Interferon-gamma - immunology; Kidney Transplantation - immunology; Kidneys; Male; Medical sciences; memory cells; Microbiology; Middle Aged; Miscellaneous; Phenotype; Receptors, CCR7 - immunology; T cell receptors; transplantation; Transplants & implants; Varicella-zoster virus; Viral diseases; Virology; Virus Activation; Human; Varicella zoster virus; effector cells; Herpesviridae; Alphaherpesvirinae; Cytokine; Recipient; Transplantation; Kidney; Virus; IFN-γ; memory cells; T-Lymphocyte; Elderly; Age; Gamma interferon
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.23427

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. J. Med. Virol. 84:2018–2025, 2012. © 2012 Wiley Periodicals, Inc.