Role of the adhesion molecule ICAM‐1 (CD54) in staphylococcal enterotoxin‐mediated cytotoxicity

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Abstract
Staphylococcal enterotoxin A (SEA) binds to major histocompatibility complex (MHC) class II molecules on target cells and directs human cytotoxic T lymphocytes (CTL) of irrelevant nominal specificity to mediate strong cytotoxicity against target cells. In this report we describe the importance of ICAM‐1(CD54) expression on the target cell in SEA‐dependent cell‐mediated cytotoxicity (SDCC), utilizing murine L cells co‐transfected with HLA‐DR and ICAM‐1. Human CTL mediated a low but significant cytotoxicity against HLA‐DR2‐and HLA‐DR7‐transfected cells after preincubation with SEA, but no reactivity towards uncoated HLA‐DR2 and HLA‐DR7 cells or SEA‐coated ICAM‐1‐transfected and untransfected L cells. In contrast, a strong cytotoxic response was mediated by CTL against L cells co‐transfected with HLA‐DR/ICAM‐1 and HLA‐DR7/ICAM‐1. Similar cytotoxic activity of the CTL was seen at a 30‐fold lower effector‐to‐target cell ratio when comparing the HLA‐DR2/ICAM‐1‐expressing cells with the HLA‐DR2‐expressing cells. SEA dose‐response analysis demonstrated that the HLA‐DR2/ICAM‐1‐expressing target cells enabled the CTL to respond to a 1000‐fold lower concentration of SEA in comparison to the HLA‐DR2‐expressing cells. CD3+CD4+ and CD3+CD8+ cytotoxic T cell lines were equally dependent on the expression of ICAM‐1 on the target cell. The strong CTL activity against HLA‐DR2/ICAM‐1‐transfected cells could be blocked by anti‐CD11a or anti‐CD18 monoclonal antibodies (mAb), but not by anti‐CD11b, anti‐CD11c, anti‐CD2 or unrelated control mAb. The great sensitivity of HLA‐DR2/ICAM‐1 expressing target cells to SDCC was strongly reduced by preincubation with various anti‐ICAM‐1 mAb but not by mAb against monomorphic HLA‐DR or murine MHC class I determinants. The result in this study clearly demonstrates that efficient re‐targeting of human CTL by SE is dependent on a proper interaction with the heterodimer CD11a/CD18 (Leu‐CAMa, LFA‐1) on the CTL and its target cell ligand ICAM‐1.

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