Cell-mediated cytotoxicity can be regulated by p53 tumor suppressor gene activity in vitro

• Published in: Biology of the cell 1995, Vol.84 (3), p.175-185
• Main Authors: Mahdi, Tarek, Tanzer, Joseph, Brizard, André, Guilhot, François, Babin, Philippe, Kitzis, Alain
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antigens, CD - analysis; Antigens, CD - biosynthesis; Apoptosis; Base Sequence; Biological and medical sciences; Cell Line; cell-mediated cytotoxicity; Cells, Cultured; Cytotoxicity, Immunologic; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Genes, p53; Humans; Immunobiology; Interferon-alpha - pharmacology; Interleukin-2 - pharmacology; Leukemia, Erythroblastic, Acute; Lymphocyte Activation; Lymphocytes - cytology; Lymphocytes - immunology; Lymphocytes - physiology; Molecular Sequence Data; Oligodeoxyribonucleotides - pharmacology; Oligonucleotides, Antisense - pharmacology; Organs and cells involved in the immune response; p53; Recombinant Proteins; RNA, Messenger - metabolism; Thionucleotides; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - biosynthesis
• ISSN: 0248-4900; 1768-322X
• DOI: 10.1016/0248-4900(96)89427-5

The wild-type human p53 tumor suppressor gene was tested for its ability to modulate cytotoxic activity of in vitro activated peripheral blood lymphocytes. Peripheral blood mononuclear cells (PBMCs) were stimulated by phytohemagglutinin (PHA), interferon α2b (IFN α2b), interleukin 2 (IL-2) or their combinations to induce cytotoxicity. This stimulation significantly increased the percentage of cells expressing p53, which was at its maximum when induced by IL-2 combined with IFN α2b. The role of p53 in the modulation of different aspects of cytotoxic activity of these cells was analyzed by studying the effects of p53 abrogation by antisense oligonucleotide (p53 AS) treatment in comparison with p53 sense or scrambled (missense) oligonucleotide (p53 S or p53 MS) treatment. We show that p53 plays a key role through induction of apoptosis in target cells (tumor necrosis factor pathway) rather than through osmolytic degeneration (perforin pathway) which is only slightly increased by p53 abrogation. Meanwhile, in vitro abrogation of p53 expression in PBL was found to be accompanied by an increase of CD8+ lymphocytes and an important increase of the CD56 ‘bright’ NK cell sub-population.