title: Unidirectional signaling triggered through 2B4 (CD244), not CD48, in murine NK cells.
abstract: Engagement of 2B4 (CD244) with CD48 results in activation, costimulation, or inhibition of NK cell activities, depending on the cell types and the stage of differentiation. In vivo, 2B4+ NK cells can interact with CD48+ NK cells and also with surrounding CD48+ hematopoietic cells. Similarly, CD48+ NK cells may be triggered by adjacent 2B4+ NK cells or other hematopoietic cells expressing 2B4, e.g., monocytes, basophils, γδ T cells, etc. As CD48 was also shown to function as an activating receptor, 2B4/CD48 binding in the settings of NK-to-NK or NK-to-non-NK cell interactions may generate bidirectional signals. To address this question, we examined the consequence of CD48 or 2B4 ligation using two experimental settings: one with target (syngeneic EL4 and allogeneic P815) cells, ectopically expressing surface 2B4 or CD48, and the other with direct cross-linking with plate-bound mAb. Here, we report that ligation of CD48 with 2B4+ EL4 or 2B4+ P815 targets, in the absence of other receptor engagement, did not alter NK cell cytotoxicity or proliferation significantly. Similarly, cross-linking of NK cells with plate-bound anti-CD48 mAb in the absence or presence of a suboptimal dose of IL-2 did not modulate NK proliferation, cytotoxicity, or cytokine production. Nonetheless, 2B4 cross-linking promoted NK cell proliferation and effector functions consistently in both settings. Therefore, our results demonstrate unequivocally that CD48 on surrounding NK or non-NK cells serves primarily as a ligand to stimulate 2B4 on the adjacent NK cells in mice.
authors.affiliation: Global Research Lab, Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, Graduate School of Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Kim
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Kim
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000071178:CD48 Antigen; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family