Diminished chemokine and cytokine-induced adhesion of CD4+T cells to extracellular matrix ligands in patients with end-stage renal failure

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the prescence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM. Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor-α-induced adhesion of CD4+T cells to ECM in a uremic milieu. Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group. Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10-11% vs. 24-29% for soluble chemokines, P<0.001; 12-13% vs. 37-39% for bound chemokines on resting cells, P<0.01; and 18-20% vs. 45-47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01). Adherence of dialysis patients' cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15-17% vs. 25-32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude. Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients' T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.