Abnormal T-cell costimulation by proteins of the extracellular matrix in human renal allografting.
T cells interact with extracellular matrix (ECM) proteins as they pass through the endothelium and move about in various microenvironments. Recent data indicate that such proteins provide strong costimulation to CD3-TCR-complex-mediated T-cell activation. Thus, ECM proteins can regulate T-cell responses via their integrin and non-integrin receptors. We have shown that the costimulating activity of interstitial ECM proteins (collagen type I, fibronectin) is abolished in renal allograft recipients treated with cyclosporin A (CsA) but not azathioprine. In contrast, cyclosporin treatment does not affect potent costimulation provided by the major component of basement membranes, collagen type IV. We suggest that these disturbances in T-cell interactions with ECM proteins caused by CsA therapy may contribute to cyclosporin-induced transplant arteriosclerosis.
Górski
A
A
Department of Immunology, Warsaw Medical School.
Mrowiec
T
T
Paczek
L
L
Stepień-Sopniewska
B
B
D001167:Arteritis / Q000139:chemically induced; D001379:Azathioprine / Q000494:pharmacology; D003094:Collagen / Q000502:physiology; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006084:Graft Rejection; D006801:Humans; D007249:Inflammation; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D011183:Postoperative Complications / Q000139:chemically induced; D011241:Prednisone / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D012077:Renal Artery / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011956:Receptors, Cell Surface; D016572:Cyclosporine; D003094:Collagen; D001379:Azathioprine; D011241:Prednisone