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 presence 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-1 beta and RANTES) and tumor necrosis factor-alpha-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-1 beta and RANTES) and to TNF-alpha 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-alpha (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-alpha 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-1 beta, RANTES and TNF-alpha. 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-alpha-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.
Zeltzer
E
E
Department of Nephrology, Sapir Medical Center, Kfar Saba, Israel.
Bernheim
J
J
Korzets
Z
Z
Zeeli
D
D
Rathaus
M
M
Mekori
Y A
YA
Hershkoviz
R
R
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016023:Integrins / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014511:Uremia / Q000276:immunology
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D016023:Integrins; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha