Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/114501
Author(s): | Resende, M Cardoso, MS Ribeiro, AR Flórido, M Borges, M Castro, AG Alves, NL Cooper, AM Appelberg, R |
Title: | Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain |
Publisher: | American Association of Immunologists |
Issue Date: | 2017 |
Abstract: | IFN-γ is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-γ reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-γ-producing cells of hematopoietic origin that were characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and NK lineage markers. The expression of IFN-γ by this population was higher in the liver and lower in the spleen. Furthermore, these cells were present in mice lacking both the Rag2 and the common γ-chain (γc) genes (Rag2-/-γc-/-), indicating their innate nature and their γc cytokine independence. Rag2-/-γc-/- mice are as resistant to Mycobacterium avium as Rag2-/- mice, whereas Rag2-/- mice lacking IFN-γ are more susceptible than either Rag2-/- or Rag2-/-γc-/- These lineage-negative CD45+/Thy1.2+ cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2-/-γc-/- animals and are adjacent to macrophages that expressed inducible NO synthase, suggesting a potential protective role for these IFN-γ-producing cells. Accordingly, Thy1.2-specific mAb administration to infected Rag2-/-γc-/- animals increased M. avium growth in the liver. Overall, our results demonstrate that a population of Thy1.2+ non-NK innate-like cells present in the liver expresses IFN-γ and can confer protection against M. avium infection in immunocompromised mice. |
Subject: | Animals Antibodies, Monoclonal/administration & dosage DNA-Binding Proteins/deficiency DNA-Binding Proteins/genetics DNA-Binding Proteins/immunology Granuloma/immunology Granuloma/microbiology Hematopoietic Stem Cells/immunology Immunity, Innate Immunocompromised Host/immunology Interferon-gamma/biosynthesis Interferon-gamma/genetics Interferon-gamma/immunology Interleukin Receptor Common gamma Subunit/deficiency Interleukin Receptor Common gamma Subunit/genetics Interleukin Receptor Common gamma Subunit/immunology Killer Cells, Natural/immunology Leukocyte Common Antigens/genetics Leukocyte Common Antigens/immunology Liver/cytology Liver/immunology Liver/microbiology Macrophages/immunology Mice Mice, Inbred C57BL Mycobacterium avium/growth & development Mycobacterium avium/immunology Nitric Oxide Synthase Type II/biosynthesis Nitric Oxide Synthase Type II/genetics Nitric Oxide Synthase Type II/immunology Spleen/cytology Spleen/immunology Thy-1 Antigens/genetics Thy-1 Antigens/immunology |
URI: | http://hdl.handle.net/10216/114501 |
Source: | The Journal of immunology, vol. 199(4), p. 1429-1439 |
Related Information: | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F89871%2F2012/PT |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | restrictedAccess |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
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2.ALVES.2017.pdf Restricted Access | 1.83 MB | Adobe PDF | Request a copy |
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