Innate IFN-gamma-Producing Cells Developing in the Absence of IL-2 Receptor Common gamma-Chain

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Resende, M (Author) Other; Cardoso, MS (Author) Other; Ribeiro, AR (Author) Other; Florido, M (Author) Other; Margarida Borges (Author) FFUP; Castro, AG (Author) Other; Alves, NL (Author) Other; Cooper, AM (Author) Other; Appelberg, R (Author) Other

Journal

Title: Journal of Immunology

Vol. 199

Pages: 1429-1439

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-00N-H8N

DOI: 10.4049/jimmunol.1601701

Abstract (EN): 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-g 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 (gamma c) genes (Rag2(-/-) gamma c(-/-)), indicating their innate nature and their gc cytokine independence. Rag2(-/-) gamma c(-/-) mice are as resistant to Mycobacterium avium as Rag2(-/-) mice, whereas Rag2(-/-) mice lacking IFN-g are more susceptible than either Rag2(-/-) or Rag2(-/-) gamma c(-/-). These lineage-negative CD45(+)/Thy1.2(+) cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2(-/-) gamma c(-/-) animals and are adjacent to macrophages that expressed inducible NO synthase, suggesting a potential protective role for these IFN-gamma-producing cells. Accordingly, Thy1.2specific mAb administration to infected Rag2(-/-) gamma c(-/-) 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-g and can confer protection against M. avium infection in immunocompromised mice.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11