HUMAN HEPATOMA-CELLS EXPRESSING MHC ANTIGENS DISPLAY ACCESSORY CELL-FUNCTION - DEPENDENCE ON LFA-1 ICAM-1 INTERACTION/

Malignant transformation of human hepatocytes is often accompanied by an increased expression of major histocompatibility complex (MHC) mole cules, but whether this phenomenon is related to an enhanced immunogen icity remains unknown. In this study, we tested the capacity of a seri es of human hepatoma cell lines to induce proliferation of allogeneic T cells in primary mixed lymphocyte tumour cultures (MLTC). These cell lines were positive for class I molecules, whereas class II molecule expression was either constitutive or inducible by treatment with inte rferon-gamma (IFN-gamma). We found that HA22T/VGH cells expressing cla ss II molecules constitutively stimulated high proliferative responses of purified CD4(+) T lymphocytes, whereas class II-negative Li7A cell s stimulated CD4(+) T-cell responses only when induced by treatment wi th IFN-gamma. HA22T/VGH and Li7A cells also exerted a significant stim ulatory activity for purified CD8(+) T cells whereas HepG2 cells, in w hich MHC class II molecules are neither constitutive nor IFN-gamma-ind ucible, were unable to induce CD4(+) and CD8(+) T-cell proliferative r esponses. Phenotypical analysis revealed that HA22T/VGH and Li7A expre ssed high levels of intracellular adhesion molecule-1 (ICAM-1) and exp eriments with blocking monoclonal antibodies (mAb) demonstrated that t his molecule played a key role in mediating the co-stimulatory functio n of hepatoma cells. In addition, HA22T/VGH cells were found to produc e mRNA for interleukin-1 (IL-1)beta and IL-6, while Li7a only produced IL-1 beta, yet both these cytokines were found to play a small part, if any, in T-cell co-activation. On the whole, these results show that hepatoma cells expressing MHC antigens and ICAM-1 are able to deliver signals necessary for activation of resting CD4(+) and CD8(+) T cells and suggest that they may actively participate in the anti-tumour imm une response.