Diminished adhesion of CD4+ T cells from dialysis patients to extracellular matrix and its components fibronectin and laminin.

Abstract

Cell-mediated immunity is impaired in uraemia. The recognition and ensuing interactions of immune cells, such as CD4+ T lymphocytes, with adhesive glycoproteins of the extra-cellular matrix (ECM) are mediated by integrins of the beta 1 subfamily. We have previously demonstrated that uraemic sera inhibit the proliferation and adhesion of normal CD4+ T cells to ECM components. In the present study, the adhesive capacity of CD4+ T lymphocytes of dialyzed patients (both haemodialysis [HD] and continuous ambulatory peritoneal dialysis [CAPD] was evaluated. 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) stimulation. In addition, cell surface expression of beta 1 integrins (VLA 4-6) was determined by FACScan analysis. 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 correlated directly with cell adhesion. Aged HD patients' T cells demonstrated increased adhesion to ECM and its ligands, whereas a reverse trend was demonstrated in the CAPD group. T cells of dialysis 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.