title: Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination.
abstract: 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 (R(2) = 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.
authors.affiliation: Infection Biology Laboratory, Department of Biomedicine, University of Basel Li Ka Shing Institute of Virology, University of Alberta, Edmonton.
authors.forename: Adrian
authors.initials: A
authors.lastname: Egli
authors.affiliation: Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, and Swiss Institute of Bioinformatics, Basel.
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Widmer
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Lisboa
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Santer
authors.affiliation: Division of Nephrology, University Hospital Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, and Swiss Institute of Bioinformatics, Basel.
authors.forename: Joerg
authors.initials: J
authors.lastname: Stelling
authors.affiliation: Division of Infectious Diseases, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Aliyah
authors.initials: A
authors.lastname: Baluch
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton.
authors.forename: Daire
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton.
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.affiliation: Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007252:Influenza Vaccines
keywords: B cells; T cells; cellular response; computational model; cytokine profile; cytokines; immunosuppression; influenza; vaccine