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 Blood, 15 January 2005, Vol. 105, No. 2, pp. 703-710.
Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-04-1537.

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Submitted April 22, 2004
Accepted August 24, 2004

Human CD1d-unrestricted NKT cells release chemokines upon Fas engagement

Martin Giroux and Francois Denis*

INRS-Institut Armand-Frappier, Laval, Quebec, Canada

* Corresponding author; email: francois.denis{at}inrs-iaf.uquebec.ca.

Attempts at inducing allograft immune privilege by enforced Fas Ligand expression have shown accelerated rejection mediated by neutrophils. While it has been proposed that Fas ligand was directly chemotactic towards neutrophils, several lines of evidence argue for an indirect recruitment mechanism. This question was addressed using in vitro migration assays using highly purified human leukocyte subsets. Granulocytes did not migrate in response to Fas engagement and required the presence of T cells expressing several Natural Killer (NK) cell markers. These rare CD8 memory T cells expressed T and NK cell markers and were not restricted to CD1d, showing that they are distinct from conventional Natural Killer T (NKT) cells. These cells were able to kill both NK sensitive and insensitive targets and secreted several CC and CXC chemokines active towards granulocytes, monocytes and NK cells upon Fas engagement. Chemotactic factor release depended on caspase activity, in the absence of NKT cell apoptosis. The ability of CD1d-unrestricted NKT cells to recruit innate immune system cells might play a role in cancer cell eradication and contribute to inflammatory diseases. francois.denis@inrs-iaf.uquebec.ca.


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