Expression of L-selectin ligands by transformed endothelial cells enhances T cell-mediated rejection.
Recent immunohistochemical studies have suggested that L-selectin ligands may be implicated in the infiltration of tumors and rejected transplants by lymphocytes. In the present study, polyoma-middle T Ag-transformed endothelial cells (H.end), which typically form in vivo immunogenic vascular tumors resembling Kaposi's sarcoma, were engineered to express L-selectin ligands by stable transfection with a cDNA encoding alpha(1,3/4)-fucosyltransferase (H.endft). The ability of these cells to form tumors in the s.c. tissues of normal and immunocompromised mice was then compared with that of H.end cells transfected with the hygromycin-resistance vector only (H. endhygro). H.endhygro cells rapidly formed local and metastatic tumors in normal syngeneic mice, leading to death within 2-3 mo postinjection. By contrast, tumors derived from H.endft cells displayed a slower rate of growth, an absence of metastasis, and marked lymphocyte infiltration. Animals bearing these tumors survived for a significantly longer duration than animals injected with H.endhygro cells. Alternatively, H.endft and H.endhygro cells formed tumors with comparable aggressiveness in immunocompromised mice, resulting in animal death within 3 wk of injection. H.endft but not H.endhygro cells supported L-selectin-dependent adhesion and cytolytic T cell activity in vitro. Taken together, our observations indicate that the in situ expression of fucosyltransferase may significantly influence the cellular immune response in endothelioma tumors. These results may be relevant in understanding the development of vascular opportunistic tumors such as Kaposi's sarcoma.
Biancone
L
L
Chair of Nephrology, Department of Internal Medicine, University of Torino, Italy.
Stamenkovic
I
I
Cantaluppi
V
V
Boccellino
M
M
De Martino
A
A
Bussolino
F
F
Camussi
G
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000276:immunology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*; D005647:Fucosyltransferases / Q000378:metabolism; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D006390:Hemangioendothelioma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000378:metabolism* / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D008024:Ligands; D009844:Oligosaccharides; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase