Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients.
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.
Litjens
Nicolle Helena Renier
NH
Department of Internal Medicine, Division of Nephrology, Erasmus Medical Center, Rotterdam, Netherlands. n.litjens@erasmusmc.nl
Huisman
Martin
M
van den Dorpel
Marinus
M
Betjes
Michiel Gerardus Henricus
MG
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
D016207:Cytokines; D006514:Hepatitis B Surface Antigens