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 ϩ T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2-and IFN-␥-producing CD4 ϩ T cells were identified as either central or effector memory CD4 ϩ 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 ϩ T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2 ϩ HBsAg-specific memory CD4 ϩ T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2-and IFN-␥-producing central memory CD4 ϩ 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 ϩ HBsAgspecific effector memory CD4 ϩ T cells produced by control subjects (0.5 Ϯ 0.2 ϫ 10 4 /L versus 8 Ϯ 3.5 ϫ 10 4 /L; P Ͻ 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 ϩ T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD. 19: 148319: -149019: , 200819: . doi: 10.1681 Patients with ESRD show clinical signs of an immune defect characterized by an increased susceptibility for infections and a decreased immune response to T cell-dependent antigens (e.g., hepatitis B vaccination). The precise mechanisms responsible for this immune defect are unknown; however, changes in T cell subsets and/or function may contribute substantially to the impaired cellular immune response, because ESRD is associated with lymphopenia occurring in the B and T lymphocyte compartment. [1][2][3] The available data on B cell function of patients with ESRD do not indicate an impaired function. 4 The functional data on peripheral T cells in patients with ESRD are conflicting and obtained by using the unfractionated bulk of circulating T cells. 1,3,5,6 Developments in T cell research and availability of various chemokine receptors, such as CCR7, have enabled a dissection of the T lymphocytes in different subsets. 7,8 The major T cell compartments that can be distinguished are the naive T cells (Tnaive; antigen inexperienced) and the antigen ex- J Am Soc Nephrol

Activation-induced CD137 is a fast assay for identification and multi-parameter flow cytometric analysis of alloreactive T cells

“…The current study did not require approval from an ethical committee according to the Dutch Medical Research Involving Human Subjects Act (WMO). PBMCs were isolated as described previously [23] and resuspended in RPMI-1640 containing glutamax (GibcoBRL, Paisley, Scotland) supplemented with 100 IU/ml penicillin, 100 μg/ml streptomycin and 10% heat-inactivated pooled human serum, referred to further as standard culture medium. HLA typing was performed by serological and DNA-based techniques according to international [American Society for Histocompatibility and Immunogenetics/European Federation for Immunogenetics (ASHI/EFI)] standards.…”

Comparing Humoral and Cellular Immune Response Against HBV Vaccine in Kidney Transplant Patients

“…During the phase of dialysis, diminished antigen-presenting cell (APC) function was reported to hamper mounting of HBV-specific humoral immunity (9), a process that might involve defective T helper cell generation (10).…”

Immunity to Diphtheria in Haemodialysis Patients

“…This is thought to be due to an immunosupressed status in this population (Litjens et al, 2008;Vacher-Coponat et al, 2008;Kaliuzhina et al, 2006). This is thought to be related to an impaired T cell activation by antigen presenting cells (Girndt et al, 1993;1995), impaired immune Responses and Antigen-Specific Memory CD4+ T Cells (Litjens et al, 2008), defects in NK cell function (Vacher-Coponat et al, 2008), immunodeficiency status manifested decrease in the number of CD3+, CD4+ and CD72+ cells and phagocytosis intensification (Kaliuzhina et al, 2006), T and B-lymphocyte abnormalities and impaired responses to T cell dependent pathogens such as hepatitis B virus (Argani and Akhtarishojaie, 2006) and endothelial dysfunction (Hussein, 2010). Opportunistic infectious disease such as toxoplasmosis has more prevalence than healthy subjects (solhjoo et al, 2010).…”