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) molecules, but whether this phenomenon is related to an enhanced immunogenicity remains unknown. In this study, we tested the capacity of a series 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 interferon-gamma (IFN-gamma). We found that HA22T/VGH cells expressing class II molecules constitutively stimulated high proliferative responses of purified CD4+ T lymphocytes, whereas class II-negative Li7A cells stimulated CD4+ T-cell responses only when induced by treatment with IFN-gamma. HA22T/VGH and Li7A cells also exerted a significant stimulatory activity for purified CD8+ T cells whereas HepG2 cells, in which MHC class II molecules are neither constitutive IFN-gamma-inducible, were unable to induce CD4+ and CD8+ T-cell proliferative responses. Phenotypical analysis revealed that HA22T/VGH and Li7A expressed high levels of intracellular adhesion molecule-1 (ICAM-1) and experiments with blocking monoclonal antibodies (mAb) demonstrated that this molecule played a key role in mediating the co-stimulatory function of hepatoma cells. In addition, HA22T/VGH cells were found to produce 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 tht hepatoma cells expression 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 immune response.
Paroli
M
M
Fondazione Andrea Cesalpino, I Clinica Medica, Università La Sapienza, Roma, Italy.
Carloni
G
G
Franco
A
A
De Petrillo
G
G
Alfani
E
E
Perrone
A
A
Barnaba
V
V
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis*; D006681:HLA-D Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D006680:HLA Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1