2B4(CD244)-mediated activation of NK cells reduces metastases of B16F10 melanoma in mice.
BACKGROUND
Natural killer (NK) cells are a third population of lymphocytes that can kill certain tumor cells. This killing is regulated by signals received through activating and inhibitory receptors. 2B4 (CD244), a member of the CD2 subset of Immunoglobulin superfamily, was identified as an activating receptor on NK cells. Interaction of 2B4 with its ligand CD48 or anti-2B4 mAb stimulates NK cell cytolytic function as well as production of INF-gamma.


METHODS
A murine tumor model was used to study the in vivo role of 2B4. 2B4 and CD48 were activated in vivo by injecting anti-2B4 and anti-CD48 monoclonal antibodies.


RESULTS
Activation of 2B4 or CD48 resulted in a five-fold reduction in tumor metastasis. IFN-gamma knockout mice had a two-fold increase in metastasis as compared to wild-type after 2B4 activation.


CONCLUSIONS
Activation of 2B4 and CD48 reduces metastasis of B16F10 melanoma cells and this anti-tumor effect involves both cytolytic function and cytokine production.
Johnson
Lori A
LA
Department of Molecular Biology and Immunology, University of North Texas Health Science Centre at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
Vaidya
Swapnil V
SV
Goldfarb
Ronald H
RH
Mathew
Porunelloor A
PA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; D018106:CD28 Antigens; C490007:Cd244a protein, mouse; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma