DIMINISHED ADHESION OF CD4-CELLS FROM DIALYSIS PATIENTS TO EXTRACELLULAR-MATRIX AND ITS COMPONENTS FIBRONECTIN AND LAMININ( T)

Background. Cell-mediated immunity is impaired in uraemia. The recogni tion and ensuing interactions of immune cells, such as CD4+ T lymphocy tes, with adhesive glycoproteins of the extra-cellular matrix (ECM) ar e mediated by integrins of the beta(1) subfamily. We have previously d emonstrated that uraemic sera inhibit the proliferation and adhesion o f normal CD4+ T cells to ECM components. In the present study, the adh esive capacity of CD4+ T lymphocytes of dialyzed patients (both haemod ialysis [HD] and continuous ambulatory peritoneal dialysis [CAPD] was evaluated. Methods. Adhesion of CD4+ T cells from dialysis patients to intact ECM and its immobilized moieties, fibronectin (FN) and laminin (LN) was measured following phorbol-12-myristate-13-acetate (PMA) sti mulation. In addition, cell surface expression of beta(1) integrins (V LA 4-6) was determined by FACScan analysis.Results. Compared to normal cells, CD4+ T cells of dialysis patients demonstrated a significantly reduced adhesion to ECM, FN and LN (27-28 vs 52-55%, P < 0.001). This decreased adhesive capacity was not normalized upon incubation of the cells with normal sera. Cell surface expression of beta(1) integrins was not modified. The inhibition of cell adhesion was more pronounced in CAPD patients (23-24% vs 29-30% in HD, P < 0.02). Serum albumin cor related directly with cell adhesion. Aged HD patients' T cells demonst rated increased adhesion to ECM and its ligands, whereas a reverse tre nd was demonstrated in the CAPD group. Conclusions. T cells of dialysi s patients exhibit abnormal adhesive activity, which may be due to an acquired cellular defect induced by uraemic milieu. CAPD patients show a greater degree of adhesion impairment, possibly due to their lower concentrations of serum albumin.