Inhibition by uraemic sera of CD4+ T-cell adhesion to extracellular matrix components

BACKGROUND.: T-cell-mediated immune responses are impaired in patients withchronic renal failure. The migration, proliferation, differentiation,biological functioning, and interaction with other T cells aremediated by cell surface adhesion proteins, which include integrins. METHODS.: To elucidate how uraemia can impair T-cell-mediated responsesin vivo, the effects of sera from uraemic patients on T-cellproliferation and adhesion to extracellular matrix (ECM) componentswere examined. RESULTS.: Preincubation of human CD4⁺ T cells with sera from undialysedand dialysed (haemodialysis or peritoneal dialysis) uraemicpatients inhibited the capacity of the cells to be stimulatedby phytohaemmagglutinin and by anti-CD3 monoclonal antibodyplus immobilized fibronectin (FN). Sera from uraemic and dialysedpatients, but not from healthy individuals, inhibited significantly,and in a dose-dependent fashion, human CD4⁺ T cell adhesionto immobilized FN and laminin (LN). The degree of inhibitionof adhesion was similar whether the sera were continuously present,even during the adhesion assay, or removed by washing. The adhesioninhibiting capacity of the uraemic sera was not due to modificationof the expression of ß1 integrins on the surfacesof the T cells. CONCLUSIONS.: These results suggest that uraemia can impair the proliferativecapacity and adhesion of immune cells, and thus may affect normalimmune processes and contribute to the overall immune deficiencyobserved in patients with renal failure.