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


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) stimulation. In addition, cell surface expression of beta 1 integrins (VLA 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 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.


CONCLUSIONS
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.
Zeltzer
E
E
Department of Nephrology, Meir Hospital, Kfar Saba, Israel.
Bernheim
J
J
Korzets
Z
Z
Rathaus
M
M
Mekori
Y A
YA
Hershkoviz
R
R
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017582:Renal Replacement Therapy
D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin