IFN-γ Acts on T Cells to Induce NK Cell Mobilization and Accumulation in Target Organs

Abstract

The mechanism(s) that regulates NK cell mobilization and the significance of this process to NK cell activity are unknown. After Con A-induced hepatitis, NK cells are mobilized from the spleen and bone marrow into the periphery in an IFN-γ-dependent fashion. Intraperitoneal administration of IFN-γ stimulates the mobilization of NK cells into the circulation, but not their cell death or proliferation. Increased number of circulating NK cells was coupled with their accumulation in the peritoneum, liver, and tumor-bearing lung tissue. Furthermore, increased number of NK cells in the lung reduced metastasis of Lewis lung carcinoma cells (3LL cell line) resulting in significantly extended NK-dependent survival. Mobilization of NK cells was specific and required the presence of T cells. Moreover, mobilization and migration of spleen NK cells in response to IFN-γ treatment is dependent on the chemokine receptor CXCR3. Mechanistic insights regarding the role of IFN-γ in the regulation of NK cell mobilization and their accumulation at sites of tumor metastasis may lead to the development of novel immunotherapy for cancer.

Parasitized Natural Killer cells do not facilitate the spread of Toxoplasma gondii to the brain

“…The percentage of NK cells in the spleen decreased from 3.75% in noninfected animals to 1.96% in infected animals after 4 dpi and from 3.6% to 1% after 7 dpi (Figure 1A,B), suggesting that NK cells may have migrated away. This is consistent with other T. gondii infection models12, 23 and with the idea that inflammation induces mobilization of NK cells from storage depots in the spleen to the blood and inflamed tissue 24. However, after 4 or 7 dpi, the percentage of NK cells was similar in the brain of noninfected and infected animals (Figure 1B).…”

Temporal Dissection of T-bet Functions

“…Recent reports (35,36) suggested that CxCR3, in addition to its critical role in recruiting T cell during allograft rejection, is also important in regulating NK cell mobilization under normal and pathogenic conditions (37). CxCR3 is also essential for NK-dependent antitumor responses in vivo (38).…”

CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection

“…It is still plausible that CXCL9 and/or CXCL10 could affect the activation of other cell subsets, including NK cells, by enhancing cytolytic activity as a result of augmented IFN-␥ production or enhanced proliferation, ultimately leading to increased antiviral activity (28,54,55). Conversely, CXCL9 and/or CXCL10 could play a role in limiting cytokine-mediated liver immunopathology.…”