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Publication : Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain.

First Author  Resende M Year  2017
Journal  J Immunol Volume  199
Issue  4 Pages  1429-1439
PubMed ID  28687660 Mgi Jnum  J:251446
Mgi Id  MGI:6099701 Doi  10.4049/jimmunol.1601701
Citation  Resende M, et al. (2017) Innate IFN-gamma-Producing Cells Developing in the Absence of IL-2 Receptor Common gamma-Chain. J Immunol 199(4):1429-1439
abstractText  IFN-gamma 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-gamma reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-gamma-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-gamma 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 gamma-chain (gammac) genes (Rag2(-/-)gammac(-/-)), indicating their innate nature and their gammac cytokine independence. Rag2(-/-)gammac(-/-) mice are as resistant to Mycobacterium avium as Rag2(-/-) mice, whereas Rag2(-/-) mice lacking IFN-gamma are more susceptible than either Rag2(-/-) or Rag2(-/-)gammac(-/-) These lineage-negative CD45(+)/Thy1.2(+) cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2(-/-)gammac(-/-) animals and are adjacent to macrophages that expressed inducible NO synthase, suggesting a potential protective role for these IFN-gamma-producing cells. Accordingly, Thy1.2-specific mAb administration to infected Rag2(-/-)gammac(-/-) 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-gamma and can confer protection against M. avium infection in immunocompromised mice.
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