Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers

Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin+ cells of stimulated CD8+ lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8+ T cell functions by comparing long-term cultures of the human CD8+ T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin+ cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ+ cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8+ T cells.

[1]  W. Hager,et al.  and s , 2019, Shallow Water Hydraulics.

[2]  Takemi Otsuki,et al.  Functional Properties of CD8+ Lymphocytes in Patients with Pleural Plaque and Malignant Mesothelioma , 2014, Journal of immunology research.

[3]  H. Matsuzaki,et al.  Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in mixed lymphocyte reaction of human peripheral blood mononuclear cells. , 2013, American journal of respiratory cell and molecular biology.

[4]  W. Marsden I and J , 2012 .

[5]  T. Otsuki,et al.  Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients. , 2011, American journal of respiratory cell and molecular biology.

[6]  T. Otsuki,et al.  Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2. , 2011, American journal of respiratory cell and molecular biology.

[7]  T. Nakano,et al.  Impairment in Cytotoxicity and Expression of NK Cell- Activating Receptors on Human NK Cells following Exposure to Asbestos Fibers , 2009, International journal of immunopathology and pharmacology.

[8]  J. Lieberman,et al.  Death by a thousand cuts: granzyme pathways of programmed cell death. , 2008, Annual review of immunology.

[9]  G. Sancini,et al.  Translocation pathways for inhaled asbestos fibers , 2008, Environmental health : a global access science source.

[10]  C. Hack,et al.  Human mast cells produce and release the cytotoxic lymphocyte associated protease granzyme B upon activation. , 2007, Molecular immunology.

[11]  R. Flavell,et al.  JNK2 negatively regulates CD8+ T cell effector function and anti‐tumor immune response , 2007, European journal of immunology.

[12]  A. Rao,et al.  Chromosome transfer activates and delineates a locus control region for perforin. , 2007, Immunity.

[13]  Robert D. Schreiber,et al.  Interferons, immunity and cancer immunoediting , 2006, Nature Reviews Immunology.

[14]  J. Virchow,et al.  Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma. , 2006, Blood.

[15]  V. Maino,et al.  Ex vivo analysis of T-cell function. , 2005, Current opinion in immunology.

[16]  A. Palucka,et al.  Dendritic cells as therapeutic vaccines against cancer , 2005, Nature Reviews Immunology.

[17]  S. Kyrtopoulos,et al.  Mutagenesis by asbestos in the lung of λ-lacI transgenic rats , 2004 .

[18]  A. Collins,et al.  Genotoxic effects of asbestos in humans. , 2004, Mutation research.

[19]  P. Henkart,et al.  Perforin and the granule exocytosis cytotoxicity pathway. , 2003, Current opinion in immunology.

[20]  T. Ley,et al.  Lymphocyte-mediated cytotoxicity. , 2003, Annual review of immunology.

[21]  F. Brière,et al.  Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. , 2002, Blood.

[22]  M. Takiguchi,et al.  Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype1 , 2002, The Journal of Immunology.

[23]  R. Dodson,et al.  Asbestos content in the lymph nodes of nonoccupationally exposed individuals. , 2000, American journal of industrial medicine.

[24]  M. Rep,et al.  Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells , 1997, The Journal of experimental medicine.

[25]  G. Guthrie,et al.  Mineral properties and their contributions to particle toxicity. , 1997, Environmental health perspectives.

[26]  A. Morgan Acid leaching studies of chrysotile asbestos from mines in the Coalinga region of California and from Quebec and British Columbia. , 1997, The Annals of occupational hygiene.

[27]  M. Klein,et al.  Phenotypic and functional separation of memory and effector human CD 8 + T cells , 1997 .

[28]  Y. Shinohara,et al.  Mineral phases and some reexamined characteristics of the International Union Against Cancer standard asbestos samples. , 1996, American journal of industrial medicine.

[29]  S. Weitzman,et al.  Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. , 1996, Cancer investigation.

[30]  H. Weill,et al.  Mesothelioma , 1995, The Lancet.

[31]  H. Asada,et al.  Establishment and characterization of the T-cell line, EBT-8 latently infected with Epstein-Barr virus from large granular lymphocyte leukemia. , 1994, Leukemia.

[32]  C. Bianchi,et al.  A Comparison of Asbestos Burden in Lung Parenchyma, Lymph Nodes, and Plaques , 1991, Annals of the New York Academy of Sciences.

[33]  F. Balkwill INTERFERONS , 1989, The Lancet.

[34]  R. Herberman,et al.  Lymphocyte-mediated cytotoxicity. , 1987, Pediatric annals.

[35]  M. Stanton,et al.  Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals. , 1981, Journal of the National Cancer Institute.

[36]  E. C. Hammond,et al.  Latency of asbestos disease among insulation workers in the United States and Canada , 1980, Cancer.

[37]  E. C. Hammond,et al.  MORTALITY EXPERIENCE OF INSULATION WORKERS IN THE UNITED STATES AND CANADA, 1943‐1976 * , 1979, Annals of the New York Academy of Sciences.

[38]  A. D. McDonald,et al.  Mesothelioma after crocidolite exposure during gas mask manufacture. , 1978, Environmental research.