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Original Article |
Correspondence to: Francesco Colucci, Laboratory for Cytokines and Lymphoid Development, Department of Immunology, The Pasteur Institute, 25 rue Dr. Roux, 75015 Paris France. Tel:33-1-4061-3664 Fax:33-1-4061-3510 E-mail:cecco{at}pasteur.fr.
The product of the protooncogene Vav1 participates in multiple signaling pathways and is a critical regulator of antigenreceptor signaling in B and T lymphocytes, but its role during in vivo natural killer (NK) cell differentiation is not known. Here we have studied NK cell development in Vav1-/- mice and found that, in contrast to T and NK-T cells, the absolute numbers of phenotypically mature NK cells were not reduced. Vav1-/- mice produced normal amounts of interferon (IFN)-
in response to Listeria monocytogenes and controlled early infection but showed reduced tumor clearance in vivo. In vitro stimulation of surface receptors in Vav1-/- NK cells resulted in normal IFN-
production but reduced tumor cell lysis. Vav1 was found to control activation of extracellular signal-regulated kinases and exocytosis of cytotoxic granules. In contrast, conjugate formation appeared to be only mildly affected, and calcium mobilization was normal in Vav1-/- NK cells. These results highlight fundamental differences between proximal signaling events in T and NK cells and suggest a functional dichotomy for Vav1 in NK cells: a role in cytotoxicity but not for IFN-
production.
Key Words: tumor clearance, Listeria infection, exocytosis, lymphoid development, cytokines
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