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Cx43-Gap Junctions Accumulate at the Cytotoxic Immunological Synapse Enabling Cytotoxic T Lymphocyte Melanoma Cell Killing.
Hofmann, Francisca; Navarrete, Mariela; Álvarez, Javiera; Guerrero, Israel; Gleisner, María Alejandra; Tittarelli, Andrés; Salazar-Onfray, Flavio.
Afiliação
  • Hofmann F; Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fcah.vega@gmail.com.
  • Navarrete M; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fcah.vega@gmail.com.
  • Álvarez J; Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. mariela.navarrete.s@gmail.com.
  • Guerrero I; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. mariela.navarrete.s@gmail.com.
  • Gleisner MA; Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. jalvarezm1011@gmail.com.
  • Tittarelli A; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. jalvarezm1011@gmail.com.
  • Salazar-Onfray F; Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. israel.guerrero.l@gmail.com.
Int J Mol Sci ; 20(18)2019 Sep 12.
Article em En | MEDLINE | ID: mdl-31547237
Upon tumor antigen recognition, cytotoxic T lymphocytes (CTLs) and target cells form specialized supramolecular structures, called cytotoxic immunological synapses, which are required for polarized delivery of cytotoxic granules. In previous reports, we described the accumulation of connexin 43 (Cx43)-formed gap junctions (GJs) at natural killer (NK) cell-tumor cell cytotoxic immunological synapse. In this report, we demonstrate the functional role of Cx43-GJs at the cytotoxic immunological synapse established between CTLs and melanoma cells during cytotoxicity. Using confocal microscopy, we evaluated Cx43 polarization to the contact site between CTLs isolated from pMEL-1 mice and B16F10 melanoma cells. We knocked down Cx43 expression in B16F10 cells and evaluated its role in the formation of functional GJs and the cytotoxic activity of CTLs, by calcein transfer and granzyme B activity assays, respectively. We found that Cx43 localizes at CTL/B16F10 intercellular contact sites via an antigen-dependent process. We also found that pMEL-1 CTLs but not wild-type naïve CD8+ T cells established functional GJs with B16F10 cells. Interestingly, we observed that Cx43-GJs were required for an efficient granzyme B activity in target B16F10 cells. Using an HLA-A2-restricted/MART-1-specific CD8+ T-cell clone, we confirmed these observations in human cells. Our results suggest that Cx43-channels are relevant components of cytotoxic immunological synapses and potentiate CTL-mediated tumor cell killing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Junções Comunicantes / Conexina 43 / Sinapses Imunológicas / Melanoma Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T Citotóxicos / Junções Comunicantes / Conexina 43 / Sinapses Imunológicas / Melanoma Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça