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

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 susceptibility to MHC-unrestricted lysis by TCR-CD3-CD16+ natural killer (NK) and TCR gamma delta + 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 gamma delta + 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 interactions increase MHC-unrestricted or CD16-mediated cytolysis of tumor cells. Anti-CD18 (LFA-1 beta) mAb inhibited MHC-unrestricted lysis of ICAM-1+ and ICAM-1- tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)