title: Serial influenza-vaccination reveals impaired maintenance of specific T-cell memory in patients with end-stage renal failure.
abstract: To investigate correlates for the well-known impaired response of haemodialysis-patients to a variety of recommended vaccinations, the induction of antigen-specific cellular and humoral immunity was characterised after influenza-vaccination in two following seasons where the identical vaccine-composition was used. Influenza-specific T-cells were flow-cytometrically characterised from whole blood of 24 healthy controls and 26 haemodialysis-patients by proliferation-assays, induction of IFN-γ and TNF-α, and maturation markers. Antibody-titres were quantified using ELISA and hemagglutination-inhibition test. Influenza-specific CD4 T-cells were recently activated CD45RO+/CD27+ Th1-cells. Specific T-cell frequencies significantly increased 1-2 weeks after the first vaccination in both controls (mean increase by 0.50±0.64%, max: 3.01%) and haemodialysis-patients (by 0.55±0.71%, max: 3.44%). Thereafter, T-cell levels continuously decreased to pre-vaccination levels within approximately 7 weeks, whereas antibody-titres were more stable over time. By 6 months, haemodialysis-patients had significantly lower precursor-frequencies of proliferating influenza-specific memory T-cells (p=0.006). In the following season, memory-maintenance in immunocompetent individuals led to a significantly less pronounced increase in cellular immunity after re-vaccination (by only 0.12±0.09%, p=0.003), whereas the vaccine induced a strong increase in a second group of vaccination-naïve controls. Of note, haemodialysis-patients responded like vaccination-naïve individuals, as they showed a strong increase in cellular immunity after re-vaccination that was as pronounced as in the year before. In conclusion, the less pronounced T-cell increase after re-vaccination in controls may indicate maintenance of sufficient immunological memory. In contrast, the more rapid loss of proliferating cells in haemodialysis-patients may represent a sign of relative immunodeficiency and contribute to an increased incidence of recurrent infectious complications.
authors.affiliation: Department of Internal Medicine IV, Saarland University, Homburg, Germany.
authors.forename: Urban
authors.initials: U
authors.lastname: Sester
authors.forename: Tina
authors.initials: T
authors.lastname: Schmidt
authors.forename: Martin K
authors.initials: MK
authors.lastname: Kuhlmann
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Gärtner
authors.forename: Heike
authors.initials: H
authors.lastname: Uhlmann-Schiffler
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology; D007251:Influenza, Human / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D007252:Influenza Vaccines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens
keywords: Chronic renal failure; Clinical immunology; Immunisation; Influenza; SEB; Staphylococcus aureus enterotoxin B; T-cells; Vaccination