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.
Giroux
Martin
M
Institut National de Recherche et de Sécurité-Institut Armand-Frappier, Laval, QC, Canada.
Denis
François
F
D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D053222:Fas Ligand Protein; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D017252:CD3 Complex; D019002:CD56 Antigen; D016827:CD8 Antigens; D018925:Chemokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor