nk cell subgroups, phenotype and functions after autologous stem cell transplantation

subkelompok sel NK, fenotipe, dan fungsi pascatransplantasi sel punca autolog

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ID: 212273
2015
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Abstract
High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotypes and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and KIR compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly up-regulated KIR2DL2/3 and KIR3DL1, whereas KIR2DL1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration.In conclusion, we describe an unusual up-regulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.
Kemoterapi dosis tinggi dengan transplantasi sel punca autolog (autoSCT) konsekutif merupakan pilihan terapi yang telah mapan bagi pasien yang menderita limfoma maligna atau mieloma multipel. Sel *natural killer* (NK) merupakan bagian penting dari surveilans imun, dan jumlah sel tersebut setelah autoSCT bersifat prediktif terhadap kesintasan bebas progresi dan kesintasan keseluruhan. Untuk meningkatkan pemahaman mengenai peran sel NK setelah autoSCT, kami meneliti berbagai subkelompok sel NK, fenotipe, serta fungsinya pada pasien yang diterapi dengan autoSCT. Segera setelah regenerasi leukosit (>1000 leukosit/μl) pasca-autoSCT, sel NK CD56++ merupakan subset sel NK utama. Secara mengejutkan, sel-sel ini menunjukkan tingkat ekspresi permukaan CD57 dan KIR yang tidak lazim tingginya dibandingkan dengan tingkat ekspresi sebelum atau pada titik waktu selanjutnya setelah autoSCT. Selain itu, sel-sel NK ini meregulasi naik KIR2DL2/3 dan KIR3DL1 secara kuat, sedangkan KIR2DL1 tetap konstan, yang mengindikasikan bahwa populasi sel ini berasal dari sel NK yang lebih imatur, bukan dari sel matur yang teraktivasi. Menariknya, sel NK sudah mampu berdegranulasi serta memproduksi IFN-γ dan MIP-1β saat berinteraksi dengan tumor pada fase awal setelah regenerasi leukosit. Kesimpulannya, kami mendeskripsikan regulasi naik yang tidak biasa dari CD57 dan KIR pada sel NK CD56++ segera setelah autoSCT. Hal yang terpenting, sel-sel NK ini kompeten secara fungsional saat berinteraksi dengan tumor pada titik waktu awal tersebut.
Reference Key
ejacobs2015frontiersnk Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Benedikt eJacobs;Benedikt eJacobs;Benedikt eJacobs;Sara eTognarelli;Sara eTognarelli;Kerstin ePoller;Peter eBader;Peter eBader;Andreas eMackensen;Evelyn eUllrich;Evelyn eUllrich;Evelyn eUllrich
Journal sudebno-meditsinskaia ekspertiza
Year 2015
DOI
10.3389/fimmu.2015.00583
URL
http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00583/full
Keywords
nk cells autologous stem cell transplantation allergy cd107a expressionimmunologic diseases

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