Flores-Romo L, Björck P, Duvert V, van Kooten C, Saeland S, Banchereau J
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
J Exp Med. 1997 Jan 20;185(2):341-9. doi: 10.1084/jem.185.2.341.
Human CD34+ multilineage progenitor cells (CD34HPC) from cord blood and bone marrow express CD40, a member of the tumor necrosis factor-receptor family present on various hematopoietic and nonhematopoietic cells. As hyper-IgM patients with mutated CD40 ligand (CD40L) exhibit neutropenia, no B cell memory, and altered T cell functions leading to severe infections, we investigated the potential role of CD40 on CD34HPC development. CD40-activated cord blood CD34HPC were found to proliferate and differentiate independently of granulocyte/macrophage colony-stimulating factor, into a cell population with prominent dendritic cell (DC) attributes including priming of allogeneic naive T cells. DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression. These features were shared by a dendritic population identified in situ in tonsillar T cell areas. Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.
来自脐带血和骨髓的人类CD34+多谱系祖细胞（CD34HPC）表达CD40，CD40是肿瘤坏死因子受体家族的一员，存在于各种造血细胞和非造血细胞上。由于携带突变型CD40配体（CD40L）的高IgM患者表现出中性粒细胞减少、无B细胞记忆以及T细胞功能改变，从而导致严重感染，因此我们研究了CD40在CD34HPC发育中的潜在作用。我们发现，CD40激活的脐带血CD34HPC能够独立于粒细胞/巨噬细胞集落刺激因子进行增殖和分化，形成具有显著树突状细胞（DC）特性的细胞群体，包括启动同种异体初始T细胞。通过CD40途径产生的DC显示出强烈的主要组织相容性复合体II类DR，但缺乏可检测到的CD1a和CD40表达。这些特征与在扁桃体T细胞区域原位鉴定出的树突状细胞群体相同。综上所述，目前的数据表明CD40在CD34HPC上具有功能，并且CD40L+细胞对其进行交联会导致DC的产生，这些DC可能在抗原驱动的对病原体入侵的反应过程中启动免疫反应，从而在造血、固有免疫和适应性免疫之间建立联系。
