Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism

Collin J. LaCasse, Nona Janikashvili, Claire B Larmonier, Darya Alizadeh, Neale Hanke, Jessica Kartchner, Elaine Situ, Sara Centuori, Michael Har-Noy, Bernard Bonnotte, Emmanuel Katsanis, Nicolas Larmonier

Research output: Contribution to journalArticle

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Abstract

Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional APCs has been the foundation for the development and use of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the nonconventional property of directly killing tumor cells. The current study investigates the regulation of murine DC cytotoxic function by T lymphocytes. We provide evidence that CD4 + Th-1, but not Th-2, Th-17 cells, or regulatory T cells, are capable of inducing DC cytotoxic function. IFN-γ was identified as the major factor responsible for Th-1-induced DC tumoricidal activity. Tumor cell killing mediated by Th-1-activated killer DCs was dependent on inducible NO synthase expression and NO production. Importantly, Th-1-activated killer DCs were capable of presenting the acquired Ags from the killed tumor cells to T lymphocytes in vitro or in vivo. These observations offer new possibilities for the application of killer DCs in cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)6310-6317
Number of pages8
JournalJournal of Immunology
Volume187
Issue number12
DOIs
StatePublished - Dec 15 2011

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Dendritic Cells
Lymphocytes
Neoplasms
Immunotherapy
Cancer Vaccines
Cytotoxic T-Lymphocytes
Adaptive Immunity
Regulatory T-Lymphocytes
Innate Immunity
Nitric Oxide Synthase
T-Lymphocytes
Population

ASJC Scopus subject areas

  • Immunology

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Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism. / LaCasse, Collin J.; Janikashvili, Nona; Larmonier, Claire B; Alizadeh, Darya; Hanke, Neale; Kartchner, Jessica; Situ, Elaine; Centuori, Sara; Har-Noy, Michael; Bonnotte, Bernard; Katsanis, Emmanuel; Larmonier, Nicolas.

In: Journal of Immunology, Vol. 187, No. 12, 15.12.2011, p. 6310-6317.

Research output: Contribution to journalArticle

LaCasse, CJ, Janikashvili, N, Larmonier, CB, Alizadeh, D, Hanke, N, Kartchner, J, Situ, E, Centuori, S, Har-Noy, M, Bonnotte, B, Katsanis, E & Larmonier, N 2011, 'Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism', Journal of Immunology, vol. 187, no. 12, pp. 6310-6317. https://doi.org/10.4049/jimmunol.1101812
LaCasse, Collin J. ; Janikashvili, Nona ; Larmonier, Claire B ; Alizadeh, Darya ; Hanke, Neale ; Kartchner, Jessica ; Situ, Elaine ; Centuori, Sara ; Har-Noy, Michael ; Bonnotte, Bernard ; Katsanis, Emmanuel ; Larmonier, Nicolas. / Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism. In: Journal of Immunology. 2011 ; Vol. 187, No. 12. pp. 6310-6317.
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