Decreased antigen-specific T-cell proliferation by moDC among hepatitis B vaccine non-responders on haemodialysis

Abstract

Patients with end-stage kidney disease, whether or not on renal replacement therapy, have an impaired immune system. This is clinically manifested by a large percentage of patients unresponsive to the standard vaccination procedure for hepatitis B virus (HBV). In this study, the immune response to HBV vaccination is related to the in vitro function of monocyte-derived dendritic cells (moDC). We demonstrate that mature moDC from nonresponders to HBV vaccination have a less mature phenotype, compared to responders and healthy volunteers, although this did not affect their allostimulatory capacity. However, proliferation of autologous T cells in the presence of tetanus toxoid and candida antigen was decreased in non-responders. Also, HLA-matched CD4+ hsp65-specific human T-cell clones showed markedly decreased proliferation in the group of non-responders. Our results indicate that impairment of moDC to stimulate antigen-specific T cells provides an explanation for the clinical immunodeficiency of patients with end-stage kidney disease.

Fig. 1

Low expression of CD83, CD86, HLA class I and II, and chemokine receptor CCR7 on mature moDC from non-responders and responders to hepatitis B vaccination. Responders (n=10) and non-responders (n=10) compared to healthy controls (n=8). Expression of cell surface antigens is represented as MFI on the Yaxes. P<0.05 is considered significant and depicted as ↔

Fig. 2

No difference between moDC from responder and non-responders in uptake of FITC-labelled albumin. Uptake of FITC-labeled albumin by immature and cytokine-induced mature moDC derived from controls (n=8), non-responders (n=9) and responders (n=9). Endocytosis was measured by flowcytometry, and is denoted as geometric mean of the fluorescents intensity±SD. ^*P<0.05 is considered significant by unpaired Student’s t-test

Fig. 3

Immature moDC from non-responders have an impaired ability to induce autologous T-cell proliferation in the presence of recall antigens. Proliferative response of autologous T cells to moDC and the recall antigens tetanus toxoid and Candida albicans. Data are analysed by Mann-Whitney U-test and are expressed in counts per minute (cpm)±SEM. P<0.05 is considered significant

Fig. 4

Immature moDC from non-responders have an impaired ability to induce T-cell proliferation in the presence of recall antigens. To exclude autologous T-cell anomalies as a cause for diminished T-cell responses upon recall antigens, autologous T cells were replaced by an HLA-matched hsp65-specific T-cell clone. Patients that were included have been immunophenotyped DR1 or DR3 (non-responders n=4; responders n=3). P=0.05 and is depicted as ^*