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Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination

Egli, Adrian ; Humar, Atul ; Widmer, Lukas A. ; Lisboa, Luiz F. ; Santer, Deanna M. ; Mueller, Thomas ; Stelling, Joerg ; Baluch, Aliyah ; O'Shea, Daire ; Houghton, Michael ; Kumar, Deepali

In: The Journal of Infectious Diseases, 2015, vol. 212, no. 1, p. 137-146

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    Titre
    • Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination
    Auteur
    • Egli, Adrian. Infection Biology Laboratory, Department of Biomedicine, University of Basel
    • Humar, Atul. Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
    • Widmer, Lukas A.. Department of Biosystems Science and Engineering, ETH Zurich, and Swiss Institute of Bioinformatics, Basel
    • Lisboa, Luiz F.. Li Ka Shing Institute of Virology, University of Alberta, Edmonton
    • Santer, Deanna M.. Li Ka Shing Institute of Virology, University of Alberta, Edmonton
    • Mueller, Thomas. Division of Nephrology, University Hospital Zurich, Switzerland
    • Stelling, Joerg. Department of Biosystems Science and Engineering, ETH Zurich, and Swiss Institute of Bioinformatics, Basel
    • Baluch, Aliyah. Division of Infectious Diseases, Moffitt Cancer Center, Tampa, Florida
    • O'Shea, Daire. Li Ka Shing Institute of Virology, University of Alberta, Edmonton
    • Houghton, Michael. Li Ka Shing Institute of Virology, University of Alberta, Edmonton
    • Kumar, Deepali. Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2015, vol. 212, no. 1, p. 137-146. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:303034
    Summary
    Background. Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression. Methods. We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage. Results. In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4+ T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4+CD4+ T cells (R2 = 0.35). High doses of MMF (≥2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4+CD4+ T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4+CD4+ T cells and HLA-DR expression on B cells captured seroconversion with high specificity. Conclusions. Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF