The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/341/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 341-350


Articles

CD40 Ligation on Human Cord Blood CD34+Hematopoietic Progenitors Induces Their Proliferation and Differentiation into Functional Dendritic Cells

Leopoldo Flores-Romo, Pia Björck, Valérie Duvert, Cees van Kooten, Sem Saeland, and Jacques Banchereau

From Schering-Plough, Laboratory for Immunological Research, Dardilly, France

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. CD40activated 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.


Address correspondence to Dr. Leopoldo Flores-Romo, Schering-Plough, 27 Chemin des Peupliers, BP 11, 69571 Dardilly, France.

1Abbreviations used in this paper: CD34HPC, human CD34 multilineage progenitor cells; CM, culture medium; DC, dendritic cells; HIM, hyper IgM; IDCs, interdigitating cells; NGFR, nerve growth-factor receptor.


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