Non-responsiveness to hepatitis B vaccination in haemodialysis patients: association with impaired TCR/CD3 antigen receptor expression regulating co-stimulatory processes in antigen presentation and recognition

The study was undertaken to evaluate the relationship betweennon-responsiveness to hepatitis B (HBV) vaccination in haemodialysedpatients and HBs antigen (Ag) presentation and recognition dependingon TCR/CD3 receptors expression. We have found that the causeof the blunted response to HBV vaccination is multifactorialand seems to be associated with the following: (1) A reducednumber of TCR/CD3 antigen receptor complexes on freshly isolateduraemic CD4 T cells, especially in non-responders. (2) The bluntedproliferative response of uraemic CD4 T cells isolated fromnon-responders and stimulated for 6 days by autologous monocytespresenting HBsAg was associated with the decreased density ofthe TCR/CD3 receptors. (3) Moreover, in uraemic non-respondersthe expression of adhesion and accessory molecules on monocytes(intercellular adhesion molecule-1/ ICAM-1, HLA-DR/Ia/) wassignificantly decreased following the culture with autologousmonocytes serving as HBsAg-presenting cells. CD4 molecules andlymphocyte function antigen-1ß /LFA-1ß/on helper-inducer T cells were increased before and after theculture. (4) These findings were also associated with a diminishedbinding capacity of IL-1ß and IL-6 to their receptorson helper-inducer T cells. (5) IL-2, IFN- and IL-4 productionwas decreased in uraemic non-responders, especially after 72h of the culture. (6) Inhibited proliferation of helper-inducerT cells in uraemic non-responders was only partially reversiblein the presence of exogenous IL-1ß, IL-6, IL-2 andIFN-. (7) HLA typing of uraemic non-responders was associatedwith extended haplotype: HLA A1, B8, DR3, DR7, DQ2.