Academic Journal
IL-15 trans-presentation promotes human NK cell development and differentiation in vivo
العنوان: | IL-15 trans-presentation promotes human NK cell development and differentiation in vivo |
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المؤلفون: | Huntington, N.D., Legrand, N., Alves, N.L., Jaron, B., Weijer, K., Plet, A., Corcuff, E., Mortier, E., Jacques, Y., Spits, H., Di Santo, J.P. |
المصدر: | Huntington , N D , Legrand , N , Alves , N L , Jaron , B , Weijer , K , Plet , A , Corcuff , E , Mortier , E , Jacques , Y , Spits , H & Di Santo , J P 2009 , ' IL-15 trans-presentation promotes human NK cell development and differentiation in vivo ' , Journal of Experimental Medicine , vol. 206 , no. 1 , pp. 25-34 . https://doi.org/10.1084/jem.20082013 |
سنة النشر: | 2009 |
المجموعة: | Universiteit van Amsterdam: Digital Academic Repository (UvA DARE) |
الوصف: | The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self-major histocompatability complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2(-/-)gamma c(-/-) mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15 receptor alpha (IL-15R alpha) significantly augmented human NK cells. IL-15-IL-15R alpha complexes induced extensive NK cell proliferation and differentiation, resulting in accumulation of CD16(+)KIR(+)NK cells, which was not uniquely dependent on enhanced survival or preferential responsiveness of this subset to IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a linear fashion from CD56(hi)CD(16)(-)KIR(-) to CD56(lo)CD16(+)KIR(-), and finally to CD56(lo)CD16(+)KIR(+). These data provide the first evidence that IL-15 trans-presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists generates a robust humanized immune system model to study human NK cells in vivo. IL-15 receptor agonists may provide therapeutic tools to improve NK cell reconstitution after bone marrow transplants, enhance graft versus leukemia |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | unknown |
Relation: | https://dare.uva.nl/personal/pure/en/publications/il15-transpresentation-promotes-human-nk-cell-development-and-differentiation-in-vivo(dffe8194-2c60-4003-bbdc-42039166257d).html |
DOI: | 10.1084/jem.20082013 |
الاتاحة: | https://dare.uva.nl/personal/pure/en/publications/il15-transpresentation-promotes-human-nk-cell-development-and-differentiation-in-vivo(dffe8194-2c60-4003-bbdc-42039166257d).html https://doi.org/10.1084/jem.20082013 https://pure.uva.nl/ws/files/763604/85199_320964.pdf |
Rights: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.53DCD136 |
قاعدة البيانات: | BASE |
DOI: | 10.1084/jem.20082013 |
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