These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Peripheral 4-1BB signaling negatively regulates NK cell development through IFN-gamma.
    Author: Choi BK, Kim YH, Kim CH, Kim MS, Kim KH, Oh HS, Lee MJ, Lee DK, Vinay DS, Kwon BS.
    Journal: J Immunol; 2010 Aug 01; 185(3):1404-11. PubMed ID: 20610645.
    Abstract:
    Stimulation of 4-1BB (CD137) was shown to produce strong anticancer effects in vivo. In contrast, 4-1BB-deficient (4-1BB(-/-)) B6 mice are remarkably resistant to tumor growth. We set out to determine the mechanisms involved in these seemingly contradictory observations. We found that the therapeutic effects of 4-1BB triggering were mainly dependent on CD8(+) T cells and partially on NK cells, whereas CD8(+) T and NK cells were equally needed to suppress tumor growth in 4-1BB(-/-) mice. Cellular analysis showed that the frequency and number of NK cells in the spleen and bone marrow were decreased by 4-1BB triggering but were increased in the absence of 4-1BB signaling in tumor-challenged mice. The 4-1BB-mediated downregulation of NK cell development was primarily dependent on IFN-gamma, which was produced by peripheral CD8(+) T and NK cells. The suppression of NK cell development by 4-1BB-mediated IFN-gamma production occurred in the bone marrow. As 4-1BB signaling increased in the periphery, more CD8(+) T cells but fewer NK cells contributed to the antitumor immunity. As 4-1BB signaling decreased, more NK cells participated in the antitumor immunity. We conclude that 4-1BB signaling results in a shift of the dominant type of immune cell in antitumor immunity from the innate NK cell to the adaptive CD8(+) T cell and that the level of IFN-gamma is critical for this 4-1BB-mediated shift.
    [Abstract] [Full Text] [Related] [New Search]