First Author | Kim EO | Year | 2010 |
Journal | J Leukoc Biol | Volume | 88 |
Issue | 4 | Pages | 707-14 |
PubMed ID | 20647560 | Mgi Jnum | J:165608 |
Mgi Id | MGI:4837809 | Doi | 10.1189/jlb.0410198 |
Citation | Kim EO, et al. (2010) Unidirectional signaling triggered through 2B4 (CD244), not CD48, in murine NK cells. J Leukoc Biol 88(4):707-14 |
abstractText | 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, gammadelta 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. |