| Autor: |
Goedegebuure, Peter S., Braakman, Eric, Segal, David M., Vreugdenhil, Rea J., Bolhuis, Reinder L. H. |
| Zdroj: |
International Immunology; Dec1990, Vol. 2 Issue 12, p1213-1220, 8p |
| Abstrakt: |
The binding of leukocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) to its natural target ligand, intercellular adhesion molecule 1 (ICAM-1) (CD54), is an important step in lymphocyte adhesion to cells and its subsequent activation. We studied whether LFA-1 – ICAM-1 interactions affect tumor cell suceptibility to MHC-unrestricted lysis by TCR−CD3−CD16 natural killer (NK) and TCRγδCD3CD16 lymphocytes. Moreover, tumor target cell susceptibility to anti-CD16 mAb-triggered lysis by TCR- NK cells was investigated. Therefore, ICAM-1 or ICAM-1 tumor cell lines were used as target cells. Two melanoma-derived cell lines expressing little or no ICAM-1 were relatively resistant to MHC-unrestricted lysis as well as anti-CD16 mAb-triggered lysis by fresh or cloned TCR NK cells. The ICAM-1 melanoma cell line was also relatively resistant to MHC-unrestricted lysis by TCR clones. Tumor necrosis factor (TNF) induced ICAM-1 expression on ICAM-1 tumor cells, and simultaneously increased target cell susceptibility to MHC-unrestricted as well as to anti-CD16 mAb-triggered lysis. This enhanced level of lysis was inhibited by anti-ICAM-1 mAb. Our data demonstrate that LFA-1–ICAM-1 interactions increase MHC-unrestricted or CD16-mediated cytolysis of tumor cells. Anti-CD18 (LFA-1β) mAb inhibited MHC-unrestricted lysis of ICAM-1 and ICAM-1 tumor cells. However, anti-CD18 mAb only blocked formation of lymphocyte–target cell conjugates with ICAM-1 but not with ICAM-1 target cells. These results suggest that LFA-1 can mediate positive as well as negative signals. Our data also show that LFA-1–ICAM-1 interactions co-activate and regulate cytotoxicity triggered via the receptor structure(s) involved in MHC-unrestricted lysis as well as via CD16. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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