Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes.
Mesothelioma cells (MMc) are considered to be weakly immunogenic and the experimental approaches attempting to induce an immune response against these cells have been disappointing. Our aim was to investigate whether MMc possess the surface accessory molecules involved in antigen presentation and whether these cells are capable of presenting recall antigens to autologous blood lymphocytes. Four primary MMc cultures were generated from malignant effusions and examined to assess whether the accessory molecules required for antigen presentation were present on their surfaces. Intercellular adhesion molecule-I (ICAM-I; CD54); class I and class II major histocompatibility complex-DR (MHCI and MHCII-DR); B7-1 (CD80.3); and B7-2 (CD86) expression by MMc was studied by immunocytochemical and/or FACScan analysis. MMc were pulsed with purified protein derivative (PPD), Tetanus toxoid (TT) and Candida albicans (CA) bodies, and incubated with autologous lymphocytes. Lymphocyte proliferation was estimated by radionucleotide incorporation. Phenotypic analysis showed the presence of MHCII-DR, ICAM-I and B7-2 on primary MMc cultures, whereas the phenotypic evaluation of 2 established MMc lines did not show the presence of the B7-1 and B7-2 molecules. In addition, MHCII-DR was detectable only after interferon gamma (IFN-gamma) stimulation. Primary MMc cultures acquired the capability to induce lymphocyte proliferation after pulse with the recall antigens. To achieve characterization of these lymphocytes, we generated a PPD-specific CD4+ T-cell clone. PPD-pulsed MMc were shown to specifically induce T-cell clone proliferation through a MHCII-DR-mediated process. We conclude that primary MMc possess the surface molecules required for antigen presentation and can present recall antigens to CD4+ lymphocytes.
Mutti
L
L
S. Maugeri Foundation, Institute for Research and Care, Pavia, Italy. cdl@intercom.it
Valle
M T
MT
Balbi
B
B
Orengo
A M
AM
Lazzaro
A
A
Alciato
P
P
Gatti
E
E
Betta
P G
PG
Pozzi
E
E
D000368:Aged; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008654:Mesothelioma / Q000276:immunology*; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D013745:Tetanus Toxoid; D014373:Tuberculin; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma