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Blood Cell Biochemistry pp 263–301Cite as

In Vitro Regulation of Dendritic Cell Development and Function

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Part of the book series: Blood Cell Biochemistry ((BLBI,volume 7))

Summary

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.

Actually, CD40/CD4OL interaction between DC and T cells (see Chapter 3) might represent a very early event, interruption of which might lead to prevention of T-cell priming. Finally, DC generated in vitro interact directly with naive B cells that are activated through their CD40 antigen, leading to enhanced growth, differentiation (IgM production), and preferential isotype switch toward IgA. Thus, in the extrafollicular area of lymphoid organs, in addition to prime naive T cells, DC might also provide costimulatory factors involved in the initiation of the primary B-cell response and in the development of humoral immunity.

In vivo administration of DC generated in vitro and loaded with antigen may ultimatly represent a powerful immunotherapy of presently uncontrolled infectious diseases and tumors.

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  1. Schering-Plough, Laboratory for Immunological Research, 69571, Dardilly, France

    Christophe Caux & Jacques Banchereau

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  1. Christophe Caux
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  1. Leukaemia Research Fund Cellular Development Unit, UMIST, Manchester, England

    Anthony D. Whetton

  2. The Medical School, University of Birmingham, Birmingham, England

    John Gordon

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Caux, C., Banchereau, J. (1996). In Vitro Regulation of Dendritic Cell Development and Function. In: Whetton, A.D., Gordon, J. (eds) Blood Cell Biochemistry. Blood Cell Biochemistry, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-31728-1_11

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