在 HLA 匹配的造血干细胞移植后的移植早期,一种不寻常的 CD56(明亮型)CD16(低表达型)自然杀伤细胞亚群占主导地位。
An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation.
作者信息
Dulphy Nicolas, Haas Philippe, Busson Marc, Belhadj Stéphanie, Peffault de Latour Régis, Robin Marie, Carmagnat Maryvonnick, Loiseau Pascale, Tamouza Ryad, Scieux Catherine, Rabian Claire, Di Santo James P, Charron Dominique, Janin Anne, Socié Gérard, Toubert Antoine
机构信息
Institut National de la Santé et de la Recherche Médicale, U662, Paris, France.
出版信息
J Immunol. 2008 Aug 1;181(3):2227-37. doi: 10.4049/jimmunol.181.3.2227.
The expansion of the cytokine-producing CD56(bright) NK cell subset is a main feature of lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated phenotypes and functions of CD56(bright) and CD56(dim) NK subsets from 43 HLA-matched non-T cell-depleted HSCT donor-recipient pairs. The early expansion of CD56(bright) NK cells gradually declined in the posttransplant period but still persisted for at least 1 year and was characterized by the emergence of an unusual CD56(bright)CD16(low) subset with an intermediate maturation profile. The activating receptors NKG2D and NKp46, but also the inhibitory receptor NKG2A, were overexpressed compared with donor CD56(bright) populations. Recipient CD56(bright) NK cells produced higher amounts of IFN-gamma than did their respective donors and were competent for degranulation. Intracellular perforin content was increased in CD56(bright) NK cells as well as in T cells compared with donors. IL-15, the levels of which were increased in the posttransplant period, is a major candidate to mediate these changes. IL-15 serum levels and intracellular T cell perforin were significantly higher in recipients with acute graft-vs-host disease. Altogether, CD56(bright) NK cells postallogeneic HSCT exhibit peculiar phenotypic and functional properties. Functional interactions between this subset and T cells may be important in shaping the immune response after HSCT.
产生细胞因子的CD56(明亮型)自然杀伤细胞亚群的扩增是异基因造血干细胞移植(HSCT)后淋巴细胞重建的主要特征。我们研究了43对HLA匹配的非T细胞去除的HSCT供受者对中CD56(明亮型)和CD56(暗淡型)自然杀伤细胞亚群的表型和功能。CD56(明亮型)自然杀伤细胞的早期扩增在移植后期逐渐下降,但至少持续1年,其特征是出现了具有中间成熟特征的异常CD56(明亮型)CD16(低表达)亚群。与供体CD56(明亮型)群体相比,活化受体NKG2D和NKp46以及抑制性受体NKG2A均过度表达。受者CD56(明亮型)自然杀伤细胞产生的IFN-γ量高于其各自的供体,并且具有脱颗粒能力。与供体相比,CD56(明亮型)自然杀伤细胞以及T细胞中的细胞内穿孔素含量增加。移植后期水平升高的IL-15是介导这些变化的主要候选者。急性移植物抗宿主病受者的IL-15血清水平和细胞内T细胞穿孔素明显更高。总之,异基因HSCT后的CD56(明亮型)自然杀伤细胞表现出特殊的表型和功能特性。该亚群与T细胞之间的功能相互作用可能在塑造HSCT后的免疫反应中起重要作用。