Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 7, Pages 1913-1923Publisher
WILEY
DOI: 10.1002/eji.200940278
Keywords
CD1d; Innate immunity; NK cells; NKT cells
Categories
Funding
- Swedish Research Council
- Swedish Cancer Foundation
- Swedish Foundation for Strategic Research
- Ake Wiberg Foundation
- Clas Groschinsky Foundation
- Jeansson Foundation
- Swedish National Board of Health and Welfare
- Swedish Physicians Against AIDS Foundation
- National Institute of Allergy and Infectious Diseases [R37AI052731]
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Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4(-) NKT cells, whereas most CD4(+) NKT cells lack this receptor. Interestingly, NKG2D 1 NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4(-) NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4(-) subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells.
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