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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
Hematopoietic Stem Cells/immunology
Immunity, Innate
Immunocompromised Host/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
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
Thy-1 Antigens/genetics
Thy-1 Antigens/immunology
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

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