Moretta Francesca, Petronelli Francesca, Lucarelli Barbarella, Pitisci Angela, Bertaina Alice, Locatelli Franco, Mingari Maria Cristina, Moretta Lorenzo, Montaldo Elisa
Department of Internal Medicine, University of Verona, Verona, Italy.
Lab. Analisi chimico-cliniche e microbiologiche, Ospedale Sacro Cuore Negrar, Verona, Italy.
Eur J Immunol. 2016 May;46(5):1271-8. doi: 10.1002/eji.201546079. Epub 2016 Feb 19.
NK cells play a central role in the haploidentical HSC transplantation (HSCT) to cure high-risk leukemias. Other innate lymphoid cells (ILCs) have been proposed to exert a protective role in graft-versus-host disease and could also contribute to anti-microbial defence and to lymphoid tissue remodeling. Thus, we investigated the ILC differentiation potential of HSCs isolated from BM, mobilized peripheral blood (PB), and umbilical cord blood (UCB). BM CD34(+) cells are enriched in lymphoid-committed precursors, while PB CD34(+) cells preferentially contain myeloid precursors. In vitro differentiation experiments revealed that the highest and the lowest CD56(+) CD161(+) ILC recovery was detected in UCB and PB HSC cultures, respectively. Among CD56(+) CD161(+) ILCs, the ratio between NK cells and ILC3s was similar for all HSC analyzed. ILC recovery in PB CD34(+) cultures was lower for G-CSF-mobilized HSCs (good mobilizers) than for G-CSF+plerixafor-mobilized HSC (poor mobilizers). Moreover, G-CSF inhibited in vitro ILC recovery and the degree of inhibition was proportional to the time of exposure to the cytokine. Thus, although all common sources of HSC for transplant differentiate towards ILCs, substantial differences exist among different sources and G-CSF may influence ILC recovery. These data offer new clues for a better understanding of the immune reconstitution after HSCT.
自然杀伤细胞（NK细胞）在单倍体相合造血干细胞移植（HSCT）治疗高危白血病中发挥着核心作用。其他固有淋巴细胞（ILC）被认为在移植物抗宿主病中发挥保护作用，并且也可能有助于抗菌防御和淋巴组织重塑。因此，我们研究了从骨髓（BM）、动员外周血（PB）和脐带血（UCB）中分离出的造血干细胞（HSC）向ILC的分化潜能。BM CD34(+)细胞富含淋巴系定向祖细胞，而PB CD34(+)细胞则优先含有髓系祖细胞。体外分化实验显示，在UCB和PB HSC培养物中分别检测到最高和最低的CD56(+) CD161(+) ILC回收率。在所有分析的HSC中，CD56(+) CD161(+) ILC中NK细胞与ILC3s的比例相似。对于粒细胞集落刺激因子（G-CSF）动员的HSC（良好动员剂），PB CD34(+)培养物中的ILC回收率低于G-CSF+普乐沙福动员的HSC（不良动员剂）。此外，G-CSF抑制体外ILC回收率，且抑制程度与细胞因子暴露时间成正比。因此，尽管移植中所有常见的HSC来源都会向ILC分化，但不同来源之间存在显著差异，并且G-CSF可能会影响ILC回收率。这些数据为更好地理解HSCT后的免疫重建提供了新线索。
