INHIBITION BY UREMIC SERA OF CD4-CELL ADHESION TO EXTRACELLULAR-MATRIX COMPONENTS( T)

Background. T-cell-mediated immune responses are impaired in patients with chronic renal failure. The migration, proliferation, differentiat ion, biological functioning, interaction with other T cells are mediat ed by cell surface adhesion proteins, which include integrins. Methods . To elucidate how uraemia can impair T-cell-mediated responses in viv o, the effects of sera from uraemic patients on T-cell proliferation a nd adhesion to extracellular matrix (ECM) components were examined. Re sults. Preincubation of human CD4(+) T cells with sera from undialysed and dialysed (haemodialysis or peritoneal dialysis) uraemic patients inhibited the capacity of the cells to be stimulated by phytohaemmaggl utinin and by anti-CD3 monoclonal antibody plus immobilized fibronecti n (FN). Sera from uraemic and dialysed patients, but not from healthy individuals, inhibited significantly, and in a dose-dependent fashion, human CD4(+) T cell adhesion to immobilized FN and laminin (LN). The degree of inhibition of adhesion was similar whether the sera were con tinuously present, even during the adhesion assay, or removed by washi ng. The adhesion inhibiting capacity of the uraemic sera was not due t o modification of the expression of beta-integrins on the surfaces of the T cells. Conclusions. These results suggest that uraemia can impai r the proliferative capacity and adhesion of immune cells, and thus ma y affect normal immune processes and contribute to the overall immune deficiency observed in patients with renal failure.