Natural killer dendritic cells have both antigen presenting and lytic function and in response to CpG produce IFN-gamma via autocrine IL-12
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Updated: Aug 9, 2026
Interview: Glycolipid Antigen Presentation by CD1d and the Therapeutic Potential of NKT cell Activation
Published on: January 1, 2008
Venu G Pillarisetty1, Steven C Katz, Joshua I Bleier
1Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Insights
Researchers discovered rare NK1.1+CD11c+ cells (NKDC) in mice that combine NK and dendritic cell (DC) functions. These NKDC cells lyse tumor cells, present antigens, and secrete cytokines, linking innate and adaptive immunity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells and dendritic cells (DCs) are key immune players.
- The potential for cells with dual NK and DC characteristics is largely unexplored.
Purpose of the Study:
- To identify and characterize novel immune cells with combined NK and DC functions.
- To investigate the functional capabilities and cytokine production of these newly identified cells.
Main Methods:
- Isolation of rare NK1.1+CD11c+ cells from various mouse tissues.
- Functional assays including tumor cell lysis and antigen presentation.
- Cytokine production analysis (IFN-gamma, IL-12) under different stimulation conditions (IL-4, IL-2, CpG).
- In vivo studies assessing NKDC numbers and T cell activation.
Main Results:
- Rare NK1.1+CD11c+ cells (NKDC) were isolated from mouse spleen, liver, lymph nodes, and thymus.
- NKDC exhibited dual functions: lysing tumor cells (NK activity) and presenting antigens to T cells (DC activity).
- NKDC produced significantly more IFN-gamma than DCs or NK cells when stimulated with IL-4 plus CpG, mediated by IL-12.
- CpG stimulation increased NKDC numbers in vivo, and transferred NKDC enhanced antigen-specific T cell activation.
Conclusions:
- NKDC represent a unique cell population bridging innate and adaptive immunity.
- Their cytotoxic, antigen-presenting, and cytokine-secreting abilities highlight their critical role in immune responses.
- NKDC are potent inducers of T cell activation and may be important targets for immunotherapy.
Abstract:
We have isolated rare cells bearing the NK cell surface marker NK1.1, as well as the dendritic cell (DC) marker CD11c, from the spleen, liver, lymph nodes, and thymus of normal mice. These cells possess both NK cell and DC function because they can lyse tumor cells and subsequently present Ags to naive Ag-specific T cells. Interestingly, in response to IL-4 plus either IL-2 or CpG, NKDC produce more IFN-gamma than do DC, or even NK cells. We determined that CpG, but not IL-2, induces NKDC to secrete IFN-gamma via the autocrine effects of IL-12. In vivo, CpG dramatically increases the number of NKDC. Furthermore, NKDC induce greater Ag-specific T cell activation than do DC after adoptive transfer. Their unique ability to lyse tumor cells, present Ags, and secrete inflammatory cytokines suggests that NKDC may play a crucial role in linking innate and adaptive immunity.
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