Schibler K R, Georgelas A, Rigaa A
Division of Neonatology/Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Acta Paediatr Suppl. 2002;91(438):9-16. doi: 10.1111/j.1651-2227.2002.tb02900.x.
To determine whether an imbalance of dendritic cell subsets might contribute to diminished adaptive host responses observed in newborn infants. It was hypothesized that the proportion of lymphoid dendritic cells would be greater than that of myeloid dendritic cells in cord blood.
To investigate this, dendritic cell subsets were evaluated in whole cord blood by flow cytometry. Circulating dendritic cells were also isolated from cord blood based on CD1c and BDCA-2 expression. Myeloid dendritic cells were also obtained by culturing cord and adult blood monocytes. Surface phenotypes of these cells were determined by flow cytometry using monoclonal antibodies directed against lineage, major histocompatibility, adhesion, co-stimulation and cytokine receptor molecules. Antigen-presenting functions of dendritic cell subsets were determined by mixed leukocyte reactions.
Circulating myeloid dendritic cells were higher in cord blood than previously reported in adult blood, whereas lymphoid dendritic cell numbers were similar between cord and adult blood. Expression of CD11c, CD45RA and CD45RO did not accurately differentiate between dendritic cell subsets circulating in cord blood. Fresh and culture-derived cord blood myeloid dendritic cells stimulated adult allogeneic leukocyte proliferation, while lymphoid dendritic cells were less effective inducers of an adult allogeneic leukocyte response. Culture-derived dendritic cells induced modest autologous cord blood leukocyte proliferation, but freshly isolated myeloid and lymphoid dendritic cells did not stimulated autologous leukocytes.
Contrary to the hypothesis, an imbalance in the ratio of circulating myeloid to lymphoid dendritic cell subsets does not exist and, therefore, does not contribute to diminished adaptive immune responses in newborn infants.
确定树突状细胞亚群的失衡是否可能导致新生儿中观察到的适应性宿主反应减弱。研究假设是脐带血中淋巴样树突状细胞的比例将高于髓样树突状细胞。
为研究此问题,通过流式细胞术评估全脐带血中的树突状细胞亚群。还基于CD1c和BDCA-2表达从脐带血中分离循环树突状细胞。髓样树突状细胞也通过培养脐带血和成人血单核细胞获得。使用针对谱系、主要组织相容性、黏附、共刺激和细胞因子受体分子的单克隆抗体,通过流式细胞术确定这些细胞的表面表型。通过混合淋巴细胞反应确定树突状细胞亚群的抗原呈递功能。
脐带血中循环的髓样树突状细胞高于先前报道的成人血液中的水平,而脐带血和成人血液中淋巴样树突状细胞的数量相似。CD11c、CD45RA和CD45RO的表达不能准确区分脐带血中循环的树突状细胞亚群。新鲜的和培养来源的脐带血髓样树突状细胞刺激成人同种异体白细胞增殖,而淋巴样树突状细胞诱导成人同种异体白细胞反应的效果较差。培养来源的树突状细胞诱导适度的自体脐带血白细胞增殖,但新鲜分离的髓样和淋巴样树突状细胞不刺激自体白细胞。
与假设相反,循环的髓样与淋巴样树突状细胞亚群的比例不存在失衡,因此不会导致新生儿适应性免疫反应减弱。