Dalle Jean-Hugues, Menezes José, Wagner Eric, Blagdon Marie, Champagne Josette, Champagne Martin A, Duval Michel
Laboratory of Immunovirology, Hôpital Sainte-Justine, Montreal, Quebec, Canada, H3T 1C5.
Pediatr Res. 2005 May;57(5 Pt 1):649-55. doi: 10.1203/01.PDR.0000156501.55431.20. Epub 2005 Feb 17.
The role of natural killer (NK) cells in hematopoietic stem cell transplantation and in the control of neonatal infections is not yet clear. Donor-versus-recipient NK cell alloreactivity was found to improve outcome in some settings of hematopoietic stem cell transplantation. We hypothesized that the role of NK cells in cord blood (CB) transplantation and neonatal infections may depend on CB NK cell maturation stage. We therefore analyzed the expression of NK cell differentiation/phenotypic markers in human CB, as well as functional properties of purified CB NK cells. CD8 and CD57 expression was lower in CB than in adult NK cells. However, the expression of other differentiation markers was similar, as was cell surface density of CD56, the percentage of late NK cell precursors, interferon-gamma production, and the proliferative response of purified NK cells to IL-2. Spontaneous cytotoxic activity of purified CB NK cells against NK-sensitive targets was low but reached adult levels after treatment with IL-15. Expression of perforin and granzyme B was higher in CB NK cells (90 versus 58% and 86 versus 69%, respectively). intercellular adhesion molecule-1 and CD161 expression was lower in CB. Surprising, fewer CB NK cells expressed L-selectin, a marker of immature NK cells. Taken together, our results suggest that CB NK cells are phenotypically and functionally mature.
自然杀伤(NK)细胞在造血干细胞移植及新生儿感染控制中的作用尚不清楚。在某些造血干细胞移植情况下,供体对受体的NK细胞同种异体反应性被发现可改善预后。我们推测NK细胞在脐血(CB)移植和新生儿感染中的作用可能取决于CB NK细胞的成熟阶段。因此,我们分析了人CB中NK细胞分化/表型标志物的表达,以及纯化的CB NK细胞的功能特性。CB中CD8和CD57的表达低于成人NK细胞。然而,其他分化标志物的表达相似,CD56的细胞表面密度、晚期NK细胞前体的百分比、干扰素-γ的产生以及纯化的NK细胞对IL-2的增殖反应也相似。纯化的CB NK细胞对NK敏感靶标的自发细胞毒性活性较低,但在用IL-15处理后达到成人水平。CB NK细胞中穿孔素和颗粒酶B的表达较高(分别为90%对58%和86%对69%)。CB中细胞间黏附分子-1和CD161的表达较低。令人惊讶的是,表达不成熟NK细胞标志物L-选择素的CB NK细胞较少。综上所述,我们的结果表明CB NK细胞在表型和功能上是成熟的。