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Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Aug 15; Vol. 199 (4), pp. 1429-1439. Date of Electronic Publication: 2017 Jul 07. - Publication Year :
- 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 <superscript>-/-</superscript> γc <superscript>-/-</superscript> ), indicating their innate nature and their γc cytokine independence. Rag2 <superscript>-/-</superscript> γc <superscript>-/-</superscript> mice are as resistant to Mycobacterium avium as Rag2 <superscript>-/-</superscript> mice, whereas Rag2 <superscript>-/-</superscript> mice lacking IFN-γ are more susceptible than either Rag2 <superscript>-/-</superscript> or Rag2 <superscript>-/-</superscript> γc <superscript>-/-</superscript> These lineage-negative CD45 <superscript>+</superscript> /Thy1.2 <superscript>+</superscript> cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2 <superscript>-/-</superscript> γc <superscript>-/-</superscript> 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 <superscript>-/-</superscript> γc <superscript>-/-</superscript> animals increased M. avium growth in the liver. Overall, our results demonstrate that a population of Thy1.2 <superscript>+</superscript> non-NK innate-like cells present in the liver expresses IFN-γ and can confer protection against M. avium infection in immunocompromised mice.<br /> (Copyright © 2017 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antibodies, Monoclonal administration & dosage
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
DNA-Binding Proteins immunology
Granuloma immunology
Granuloma microbiology
Immunocompromised Host immunology
Interferon-gamma immunology
Interleukin Receptor Common gamma Subunit deficiency
Interleukin Receptor Common gamma Subunit genetics
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
Hematopoietic Stem Cells immunology
Immunity, Innate
Interferon-gamma biosynthesis
Interferon-gamma genetics
Interleukin Receptor Common gamma Subunit immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 199
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 28687660
- Full Text :
- https://doi.org/10.4049/jimmunol.1601701