title: Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients.
abstract: Serologic responses to T cell-dependent vaccinations are severely attenuated in patients with ESRD, but the reasons for this is unknown. In this study, a detailed analysis of antigen-specific T cell responses was performed. Patients on hemodialysis and age- and gender-matched healthy control subjects were vaccinated with hepatitis B surface antigen (HBsAg), antigen-specific CD4(+) T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2-and IFN-gamma-producing CD4(+) T cells were identified as either central or effector memory CD4(+) T cells using antibodies directed against CD45RO and the chemokine receptor CCR7. Control subjects mounted a memory T cell response comprising both central and effector memory CD4(+) T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2(+) HBsAg-specific memory CD4(+) T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2-and IFN-gamma-producing central memory CD4(+) T cells, but their maximal responses were similar to those of control subjects. In contrast, patients with ESRD produced only 6.3% of the IL-2(+) HBsAg-specific effector memory CD4(+) T cells produced by control subjects (0.5 +/- 0.2 x 10(4)/L versus 8 +/- 3.5 x 10(4)/L; P < 0.001), and this impaired response correlated with antigen-specific T cell proliferation and anti-HBsAg IgG titers. In conclusion, the production of antigen-specific effector memory CD4(+) T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Erasmus Medical Center, Rotterdam, Netherlands. n.litjens@erasmusmc.nl
authors.forename: Nicolle Helena Renier
authors.initials: NH
authors.lastname: Litjens
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.forename: Marinus
authors.initials: M
authors.lastname: van den Dorpel
authors.forename: Michiel Gerardus Henricus
authors.initials: MG
authors.lastname: Betjes
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016022:Case-Control Studies; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014611:Vaccination
chemical_list: D016207:Cytokines; D006514:Hepatitis B Surface Antigens