Liu E, Tu W, Law H K, Lau Y L
Department of Paediatrics, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Br J Haematol. 2001 Apr;113(1):240-6. doi: 10.1046/j.1365-2141.2001.02720.x.
Dendritic cells are critical for the induction of both primary immune responses and immunological tolerance, as well as for the regulation of T-helper 1 (Th1) and 2 (Th2) immune responses. As neonates are notably deficient in Th1 response and cord blood transplantation is noted to result in less graft-versus-host disease (GvHD), we compared the phenotypic and functional characteristics of monocyte-derived dendritic cells (DCs) that favour Th1 development from cord blood and adult peripheral blood to understand the underlying mechanisms of these observations. Our results showed that: (1) after culture for 7 d with interleukin (IL)-4 and granulocyte--macrophage colony-stimulating factor (GM-CSF), cord blood monocytes generated less CD1a(+) cells than adult peripheral blood monocytes, and the CD1a+ cell percentage decreased thereafter; (2) compared with adult blood DCs, cord blood DCs had reduced intensity of expression of CD1a and MHC class II molecules, but the expression levels of CD11c and CD86 were similar; (3) the endocytotic ability of cord blood DCs was reduced compared with adult blood DCs, and this function was related to reduced mannose receptor (MR)-positive cells; (4) furthermore, the ability of cord blood DCs to stimulate CD3(+) T cells in an allogeneic mixed lymphocyte reaction was significantly lower than that of adult blood DCs. These results suggested that the dysfunction of cord blood monocytes in differentiating into professional DCs will affect the activation of naive T cells, especially Th1 development, and may be related to the susceptibility to different infections in the neonates, as well as the lower incidence of GvHD in cord blood transplantation.
树突状细胞对于启动原发性免疫反应和诱导免疫耐受至关重要,同时也参与调节辅助性T细胞1(Th1)和辅助性T细胞2(Th2)免疫反应。由于新生儿的Th1反应明显不足,且脐血移植导致的移植物抗宿主病(GvHD)较少,我们比较了源自脐血和成人外周血、倾向于Th1发育的单核细胞衍生树突状细胞(DCs)的表型和功能特征,以了解这些现象背后的机制。我们的结果表明:(1)在白细胞介素(IL)-4和粒细胞-巨噬细胞集落刺激因子(GM-CSF)培养7天后,脐血单核细胞产生的CD1a(+)细胞比成人外周血单核细胞少,且此后CD1a+细胞百分比下降;(2)与成人血液DCs相比,脐血DCs的CD1a和MHC II类分子表达强度降低,但CD11c和CD86的表达水平相似;(3)与成人血液DCs相比,脐血DCs的内吞能力降低,且该功能与甘露糖受体(MR)阳性细胞减少有关;(4)此外,脐血DCs在同种异体混合淋巴细胞反应中刺激CD3(+) T细胞的能力明显低于成人血液DCs。这些结果表明,脐血单核细胞分化为专职DCs的功能障碍会影响幼稚T细胞的激活,尤其是Th1的发育,这可能与新生儿对不同感染的易感性以及脐血移植中GvHD发病率较低有关。