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

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 and the common γ-chain (γc) genes (Rag2γc), indicating their innate nature and their γc cytokine independence. Rag2γc mice are as resistant to as Rag2 mice, whereas Rag2 mice lacking IFN-γ are more susceptible than either or Rag2γc These lineage-negative CD45/Thy1.2 cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2γc 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 Rag2γc animals increased 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 infection in immunocompromised mice.

Control of primary mouse cytomegalovirus infection in lung nodular inflammatory foci by cooperation of interferon-gamma expressing CD4 and CD8 T cells

“…In absence of T cells, the secretion of these two molecules, most probably by NK cells, gains more importance in controlling the virus. However, it is likely that in Rag2 -/- and Rag2 -/- Il2rg -/- mice IFNγ is also produced by cells that do not express classical NK cell biomarkers [ 35 ].…”

“…In fact, we found NK cells to be the major population of lymphocytes able to secrete IFNγ at 5 dpi. Notably, an IFNγ-producing cell population lacking T and NK cell surface markers has been identified in Rag1 -/- and Rag2 -/- Il2rg -/- mice [ 35 ]. Furthermore, the secretion of perforin might be crucial for the NK cell mediated control, since we found increased virus loads in perforin-deficient mice while this effect was apparently not T cell-mediated.…”

NK Cell–Derived IFN-γ Protects against Nontuberculous Mycobacterial Lung Infection

“…Many cases of severe and disseminated NTM infection in which tuberculosis symptoms are absent also frequently occur in immunocompetent individuals of all ages (18), suggesting the existence of distinct but partially overlapping roles for IFN-g-related immunity in the control of infection caused by M. tuberculosis and NTM (17,19). Although the effects of NK cells and IFN-g in the immune response against Mycobacterium avium infection have been studied in the past (20)(21)(22), the role of IFN-g and NK cells in response to M. kansasii at early stages of NTM infection remains unclear.…”

Potential Novel Risk Factor for Breast Cancer: Toxocara canis Infection Increases Tumor Size Due to Modulation of the Tumor Immune Microenvironment

“…canis mice, the IFN-γ levels were unchanged with respect to non-infected mice. This may be because other hematopoietic cells, such as NK and CD4 + T cells, also produce IFN-γ within the tumor (39). The larger tumor size in the T. canis group could be related to the reduction in CD8 + T cell infiltration into the tumor, associated with deficient local recruitment.…”