CD1d-unrestricted human NKT cells release chemokines upon Fas engagement

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 toward neutrophils, several lines of evidence argue for an indirect recruitment mechanism. This question was addressed by using in vitro migration assays that used 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 toward 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.