Showing papers by "Christophe Caux published in 1996"

CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.

Abstract: Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.

In Vitro Regulation of Dendritic Cell Development and Function

Abstract: Human and murine dendritic cells (DC) can now be generated in vitro in large numbers by culturing progenitor cells. The establishment of such culture systems will allow clarification of the relationship between different DC populations and monocytes. In all studies, granulocyte—macrophage colony-stimulating factor (GM-CSF) has been required for the generation of DC, suggesting a crucial role for this hematopoietic growth factor during the ontogeny of the DC lineage. Those DC generated in vitro represent interesting models for studying the function of DC. Such studies established that immature DC precursors are able to phagocytose particles much more efficiently than the mature DC. These DC generated in vitro induce, after antigen loading and injection into mice, antigen-specific immune responses. Human DC generated by culturing monocytes with GM-CSF and IL-4 capture macromolecules through high-rate macropinocytosis. Human DC can also be generated by culturing CD34+ hematopoietic progenitors in the presence of GM-CSF, and further addition of TNF-α results in a strong increase of DC yield. These cultured human DC are able to prime naive T cells, a phenomenon that involves interactions between CD80/CD86 on DC and CD28 on T cells. Interestingly, DC express a functional CD40 antigen whose triggering up-regulates expression of CD80 and CD86 and induces cytokine secretion.

In vitro regulation of development and function of dendritic cells

Abstract: Dendritic cells (DC) are professional antigen presenting cells which are required for the initiation of immune responses. They are characterized by the expression of high levels of MHC class II products and an unusual dendritic shape. Although found in all organs, DC are present at trace level making tedious their purification and functional studies. Human DC can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNFalfa during 12 days [Caux et al (1992) Nature 360 : 258].