Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44.

Blood 2005 Sep 7;106(6):2076-82. Epub 2005 Jun 7.

Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA.

Natural killer (NK) cell-mediated cytotoxicity is triggered by multiple activating receptors associated with the signaling adaptor protein DNAX activation protein 12/killer cell-activating receptor-associated protein (DAP12/KARAP). Here, we show that one of these receptors, NKp44, is present on a subset of natural interferon-producing cells (IPCs) in tonsils. NKp44 expression can also be induced on blood IPCs after in vitro culture with interleukin 3 (IL-3). Crosslinking of NKp44 does not trigger IPC-mediated cytotoxicity but, paradoxically, inhibits interferon alpha (IFN-alpha) production by IPCs in response to cytosine-phosphate-guanosine (CpG) oligonucleotides. We find that IPCs in tonsils are in close contact with CD8+ T cells and demonstrate that a subset of memory CD8+ T cells produces IL-3. Therefore, IL-3-mediated induction of NKp44 on IPCs may be an important component of the ongoing crosstalk between the innate and adaptive immune response that allows memory CD8+ T cells to control the IPC response to virus.

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2004-12-4802DOI Listing
September 2005
3 Reads

Publication Analysis

Top Keywords

cd8+ cells
12
natural interferon-producing
8
memory cd8+
8
ipcs tonsils
8
interferon-producing cells
8
nkp44
5
ipcs
5
cells
5
paradoxically inhibits
4
alpha ifn-alpha
4
interferon alpha
4
inhibits interferon
4
cpg oligonucleotides
4
production ipcs
4
cytosine-phosphate-guanosine cpg
4
cytotoxicity paradoxically
4
ipcs response
4
response cytosine-phosphate-guanosine
4
ifn-alpha production
4
nkp44 trigger
4

References

(Supplied by CrossRef)

Similar Publications