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Post‐transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV‐specific T‐cell anergy. In the ATHENA‐study, de‐novo everolimus (EVR) with reduced‐exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA‐study completing the 12‐month visit on‐treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV‐specific CD4 T cells were determined after stimulation with CMV‐antigen, and cytokine‐profiles and various T‐cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC‐treated patients had CMV‐infections, no such events were reported in EVR‐treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV‐specific T cells, their median expression of CTLA‐4 and PD‐1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA‐4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV‐specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR‐treated patients retained CMV‐specific T‐cell functionality, which may contribute to enhanced protection against CMV infections. [ABSTRACT FROM AUTHOR]

VZV‐reactivation may lead to symptomatic central nervous system (CNS) diseases, but identification of VZV as causative pathogen of CNS‐diseases is challenging. This study was performed to characterize VZV‐specific T cells from cerebrospinal fluid (CSF) and blood of patients with active CNS‐disease and to determine whether this may improve differential diagnosis. 27 patients with pleocytosis in the CSF were recruited and classified into three groups (10 VZV‐related, 10 non‐VZV‐related, 7 unclear). VZV‐specific CD4+ T cells were quantified in CSF and blood after simultaneous stimulation with a VZV‐antigen lysate and detection of cytokines (IFN‐γ, IL‐2, TNF‐α) and CTLA‐4. Polyclonal stimulation served as positive control. VZV‐specific CD4+ T‐cell frequencies were highest in both CSF (p = 0.0001) and blood (p = 0.011) of patients with VZV‐infection, and were enriched at the site of infection (p = 0.002). While cytokine‐expression profiles only showed minor differences between the groups, CTLA‐4‐expression levels on VZV‐specific T cells from CSF and blood were significantly increased in VZV‐related CNS‐infections (p = 0.0002 and p<0.0001) and clearly identified VZV‐related CNS‐diseases (100% sensitivity and 100% specificity). Polyclonally stimulated T cells did not show any quantitative and phenotypical differences between the groups. Increased frequency and CTLA‐4‐expression of VZV‐specific T cells from CSF or blood are specifically found in patients with VZV‐related CNS‐infection. [ABSTRACT FROM AUTHOR]

Antigen-specific antibodies are well characterized after vaccination with pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular immunity toward pandemic H1N1 after vaccination and infection and cross-reactivities toward seasonal antigens is limited. Nineteen individuals were vaccinated with the pandemic H1N1 vaccine. Among those, ten had been prevaccinated against seasonal influenza. CD4+ T cells specific for pandemic H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry and ELISA/neutralization assays, respectively. In addition, seven patients with acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination induced a strong 4.63-fold ( IQR 4.16) increase in antigen-specific CD4+ T cells that was more pronounced in individuals not prevaccinated with seasonal influenza ( p = 0.01). T-cell levels toward seasonal vaccine concomitantly rose by 2.71-fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a less pronounced increase in specific antibodies. Influenza-specific T cells in vaccinees had a Th1 phenotype mainly coexpressing IFN-γ and IL-2, whereas patients with active pandemic influenza showed a shift toward cells predominantly expressing IFN-γ. In conclusion, T cells toward seasonal influenza antigens cross-react with pandemic H1N1 antigens and affect induction of specific T cells after pandemic influenza vaccination. In addition, the cytokine patterns of specific T cells during acute H1N1 infection and after vaccination differ, and the predominantly dual-positive cytokine profile of vaccine-induced T cells suggests sufficient functionality to confer successful virus control. [ABSTRACT FROM AUTHOR]

Antigen-specific antibodies are well characterized after vaccination with pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular immunity toward pandemic H1N1 after vaccination and infection and cross-reactivities toward seasonal antigens is limited. Nineteen individuals were vaccinated with the pandemic H1N1 vaccine. Among those, ten had been prevaccinated against seasonal influenza. CD4(+) T cells specific for pandemic H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry and ELISA/neutralization assays, respectively. In addition, seven patients with acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination induced a strong 4.63-fold (IQR 4.16) increase in antigen-specific CD4(+) T cells that was more pronounced in individuals not prevaccinated with seasonal influenza (p = 0.01). T-cell levels toward seasonal vaccine concomitantly rose by 2.71-fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a less pronounced increase in specific antibodies. Influenza-specific T cells in vaccinees had a Th1 phenotype mainly coexpressing IFN-γ and IL-2, whereas patients with active pandemic influenza showed a shift toward cells predominantly expressing IFN-γ. In conclusion, T cells toward seasonal influenza antigens cross-react with pandemic H1N1 antigens and affect induction of specific T cells after pandemic influenza vaccination. In addition, the cytokine patterns of specific T cells during acute H1N1 infection and after vaccination differ, and the predominantly dual-positive cytokine profile of vaccine-induced T cells suggests sufficient functionality to confer successful virus control., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)