Publicação
Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain
| Resumo: | 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. |
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| Autores principais: | Resende, Mariana |
| Outros Autores: | Cardoso, Marcos S.; Ribeiro, Ana R.; Flórido, Manuela; Borges, Margarida; Castro, António G.; Alves, Nuno L.; Cooper, Andrea M.; Appelberg, Rui |
| Assunto: | Ciências Médicas::Medicina Básica |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | 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. |
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