Inhibition by uraemic sera of CD4+ T-cell adhesion to extracellular matrix components.
BACKGROUND
T-cell-mediated immune responses are impaired in patients with chronic renal failure. The migration, proliferation, differentiation, biological functioning, and interaction with other T cells are mediated by cell surface adhesion proteins, which include integrins.


METHODS
To elucidate how uraemia can impair T-cell-mediated responses in vivo, the effects of sera from uraemic patients on T-cell proliferation and adhesion to extracellular matrix (ECM) components were examined.


RESULTS
Preincubation of human CD4+ T cells with sera from undialysed and dialysed (haemodialysis or peritoneal dialysis) uraemic patients inhibited the capacity of the cells to be stimulated by phytohaemmagglutinin and by anti-CD3 monoclonal antibody plus immobilized fibronectin (FN). Sera from uraemic and dialysed patients, but not from healthy individuals, inhibited significantly, and in a dose-dependent fashion, human CD4+ T cell adhesion to immobilized FN and laminin (LN). The degree of inhibition of adhesion was similar whether the sera were continuously present, even during the adhesion assay, or removed by washing. The adhesion inhibiting capacity of the uraemic sera was not due to modification of the expression of beta 1 integrins on the surfaces of the T cells.


CONCLUSIONS
These results suggest that uraemia can impair the proliferative capacity and adhesion of immune cells, and thus may affect normal immune processes and contribute to the overall immune deficiency observed in patients with renal failure.
Hershkoviz
R
R
Department of Internal Medicine, Sapir Medical Center, Kfar Saba, Israel.
Korzets
Z
Z
Rathaus
M
M
Gilat
D
D
Drucker
I
I
Mekori
Y A
YA
Bernheim
J
J
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D014511:Uremia / Q000097:blood* / Q000276:immunology / Q000473:pathology
D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin