International Immunology, Vol. 2, No. 12, pp. 1213-1220,December 1990
© 1990 Japanese Society for Immunology
Lymphocyte leukocyte function-associated antigen 1 interacting with target cell intercellular adhesion molecule 1 co-activates cytolysis triggered via CD16 or the receptor involved in major histocompatibility antigen-unrestricted lysis
1 Department of Immunology, Dr Daniel den Hoed Cancer Center Rotterdam, The Netherlands
2Present address: Norris Cancer Hospital and Research Institute, Los Angeles, California, USA
3 Institute of Applied Radiobiology and Immunology, TNO Health Organisation Rijswijk, The Netherlands
4 Experimental Immunology Branch, National Cancer Institute Bethesda, MD, USA
Correspondence to: Correspondence to: R. L. H. Bolhuis, Dr Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands
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 TCR
+CD3+CD16+/– 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-1ß) 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.
Keywords: LFA-1, ICAM-1, MCH-unrestricted lysis
Received 2 April 1990, accepted 10 September 1990.