Varicella zoster virus (VZV) establishes lifelong persistence and immunocompromised patients such as hemodialysis and transplant recipients are at high risk for virus reactivation presenting as herpes zoster. To identify immunologic parameters associated with VZV-reactivation, T-cell immunity and IgG responses towards VZV were characterized in 42 immunocompromised and immunocompetent patients with acute herpes zoster and compared to 90 patients and controls without VZV reactivation.

VZV-specific CD4 T cells were analyzed after whole blood stimulation with VZV-lysate using intracellular staining for IFNΓ, IL-2, and TNFΑ. CD127, CTLA-4 and PD1 were chosen as markers for functional anergy. Stimulation with superantigen SEB served as control. IgG titers were assessed using standard ELISA.

VZV-specific CD4 T cells of non-symptomatic immunocompetent controls showed median frequencies of 0.15% (0.03-0.29%), were predominantly expressing all three cytokines (median 54.0%, IQR 9.8%; IFNΓ-single positive cells: median 5.2%, IQR 4.0%), had low CTLA-4 (MFI 1081±654) and PD1 expression (MFI 215±94) and were predominantly CD127 positive (96.0±6.2%) Non-symptomatic immunocompromised patients had similar T-cell properties, although median frequencies (p=0.02) and percentages of multifunctional VZV-specific cells (p=0.15) were slightly lower. In contrast, both immunocompetent and immunocompromised patients with acute zoster had elevated IgG titers (median 7064 IU/L, IQR 1896 IU/L) as well as frequencies of VZV-specific CD4 T-cells (median 0.48%, IQR 0.65%). The cytokine-profile of VZV-specific T cells was shifted towards IFNΓ-single positive cells (25.5%). Furthermore, T-cells showed a significant increase in CTLA-4 and PD1 expression, and a concomitant decrease in CD127 expression. SEB-reactive T-cell properties did not differ from non-symptomatic individuals. Interestingly, T cells analysed >3 months after acute reactivation reverted back to the phenotype observed in non-symptomatic individuals.

Conclusion: VZV-specific CD4 T cells in patients with acute herpes zoster are elevated in frequencies and bear typical features of anergic cells such as increased expression of CTLA-4 and PD-1, decreased expression of CD127, and restricted functionality. This phenotype may be applied for monitoring infectious complications in patients at risk.

« Back to 2013 American Transplant Congress