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

Peter S. Goedegebuure, Eric Braakman, David M. Segal, Rea J. Vreugdenhil, Reinder L.H. Bolhuis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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 TCRγδ+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-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.

Original languageEnglish
Pages (from-to)1213-1220
Number of pages8
JournalInternational Immunology
Volume2
Issue number12
DOIs
StatePublished - Dec 1990

Keywords

  • ICAM-1
  • LFA-1
  • MCH-unrestricted lysis

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