| First Author | Lee GA | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 3 | Pages | 1212-21 |
| PubMed ID | 21715685 | Mgi Jnum | J:179181 |
| Mgi Id | MGI:5301238 | Doi | 10.4049/jimmunol.1100331 |
| Citation | Lee GA, et al. (2011) Different NK cell developmental events require different levels of IL-15 trans-presentation. J Immunol 187(3):1212-21 |
| abstractText | NK cell development requires IL-15, which is "trans-presented" to IL-15Rbetagamma on NK cells by IL-15Ralpha on other cells. In this study, we report that different levels of IL-15 trans-presentation are required for different NK cell developmental events to reach full maturation status. Because the IL-15Ralpha intracellular domain has the capacity to recruit signaling molecules, we generated knockin and transgenic (Tg) mice that lack the intracellular domain to assess the role of the IL-15 trans-presentation level independent of the function of this domain. The level of IL-15Ralpha on various cells of these mice follows the order WT > Tg6 > knockin > Tg1 >/= knockout. Bone marrow (BM)-derived dendritic cells prepared from these mice induced Stat5 phosphorylation in NK cells. The level of phospho-Stat5 correlated with the level of IL-15Ralpha on BMDCs, thus offering the opportunity to study quantitative effects of IL-15 trans-presentation on NK cell development in vivo. We found that NK cell homeostasis, mature NK cell differentiation, and acquisition of Ly49 receptor and effector functions require different levels of IL-15 trans-presentation input to achieve full status. All NK cell developmental events examined were quantitatively regulated by the IL-15Ralpha level of BM-derived and radiation-resistant accessory cells, but not by IL-15Ralpha of NK cells. We also found that IL-15Ralpha of radiation-resistant cells was more potent than IL-15Ralpha of BM-derived accessory cells in support of stage 2 to stage 3 splenic mNK differentiation. In summary, each examined developmental event required a particular level of IL-15 trans-presentation by accessory cells. |
