Journal
BLOOD
Volume 107, Issue 4, Pages 1342-1351Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-08-3485
Keywords
-
Categories
Funding
- NCI NIH HHS [P01-CA09296-01] Funding Source: Medline
- NIDDK NIH HHS [5T32DK07 074, R01-DK58897, P30-DK42086] Funding Source: Medline
- PHS HHS [R01-062026] Funding Source: Medline
Ask authors/readers for more resources
Natural killer (NK) cells are generally reported as innate effector cells for killing virally infected and transformed cells. It is unclear how NK cells evoke adaptive immunity to eradicate tumors. We now demonstrate that the TNF superfamily member, LIGHT, known as TNFSF14 and a T-cell costimulatory molecule, is a critical ligand for the activation of NK cells. Herpesvirus entry mediator (HVEM) is expressed on NK cells, and its engagement with LIGHT mediates NK-cell activation. dent manner. Both NK and CD8(+) cells are essential but not sufficient for the rejection of tumors because mice lacking either population fail to reject the tumor. Interestingly, activated NK cells do not kill tumors directly but can facilitate the priming of tumor-specific CD8(+) T cells in an IFN-gamma-dependent manner. Conversely, intratumor depletion of either NK cells or IFN-gamma during tumor progression disrupts CD8(+) cell-mediated tumor rejection, suggesting that the tumor is the essential site for the crosstalk between NK and CD8(+) cells. Furthermore, IFNG-deficient NK cells fail to effectively activate CD8(+) T cells, suggesting IFN-gamma plays an important role in NK-mediated activation of cytotoxic T lymphocytes (CTLs). Our findings establish a direct role for LIGHT in NK activation/expansion and a critical helper role of activated NK cells in priming CD8(+) T cells and breaking T-cell tolerance at the tumor site.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available