| Summary: | 博士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 99 === Natural killer (NK) cell development requires IL-15, which is “trans-presented” to IL-15R???non NK cells by IL-15R? on neighboring cells. In this study, we found that different levels of IL-15 trans-presentation are required for different NK cell developmental events to reach full maturation status. Because the IL-15R? intracellular (IC) domain has the capacity to recruit signaling molecules, we generated knock-in (KI) and transgenic (Tg) mice that lack the IC domain to assess independently the role of the IL-15 trans-presentation level. The level of IL-15R? on various cells of these mice follows the order WT > Tg6 > KI > Tg1 ≥ KO. Bone marrow-derived dendritic cells (BMDCs) prepared from these mice induced Stat5 phosphorylation in NK cells. The level of phospho-Stat5 correlated with the level of IL-15R? 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-15R? level of BM-derived and radiation-resistant accessory cells, but not by IL-15R??nof NK cells?|?nWe also found that IL-15R? of radiation-resistant cells was more potent than IL-15R? of BM-derived accessory cells in the 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.
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