Trends in Immunology

Trends in Immunology

Volume 22, Issue 12, 1 December 2001, Pages 691-700
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Review
Origin and differentiation of dendritic cells

https://doi.org/10.1016/S1471-4906(01)02059-2Get rights and content

Abstract

Despite extensive, recent research on the development of dendritic cells (DCs), their origin is a controversial issue in immunology, with important implications regarding their use in cancer immunotherapy. Although, under defined experimental conditions, DCs can be generated from myeloid or lymphoid precursors, the differentiation pathways that generate DCs in vivo remain unknown largely. Indeed, experimental results suggest that the in vivo differentiation of a particular DC subpopulation could be unrelated to its possible experimental generation. Nevertheless, the analysis of DC differentiation by in vivo and in vitro experimental systems could provide important insights into the control of the physiological development of DCs and constitutes the basis of a model of common DC differentiation that we propose.

Section snippets

Myeloid-derived DCs

Evidence for a myeloid DC lineage derives, in part, from human and mouse in vitro DC differentiation assays, in which DCs were generated from monocytes or intermediate myeloid precursors that retained the capacity to generate macrophages. Bipotential macrophage–DC precursors have been characterized in mouse bone marrow (BM) 4, and in vivo differentiation of dermal CD11b+F4/80− phagocytic cells, considered to be monocytes, into DCs upon migration to the lymph nodes has been reported 5.

Lymphoid-derived DCs

The first

Mouse DC differentiation

Most of the relevant information relating to the in vivo development of murine DCs has been reported in the previous section. Different experimental approaches have been designed to analyze the development of murine DCs in vitro, which involve different hematopoietic precursors, the use of diverse DC differentiation- and/or maturation-inducing mediators and different culture protocols. Most of the relevant data on this topic is summarized in Fig. 2. Most methods developed for generating DCs in

Differentiation of human DCs

In vitro studies of the differentiation of human DCs have been influenced greatly by the aim of optimizing culture systems to allow an efficient production of DCs for use in cancer immunotherapy. Additional studies have been conducted simultaneously to explore the mechanisms controlling different generation pathways for human DCs. The essential information derived from these studies is summarized in Fig. 4. Two main protocols to generate DCs, from either monocytes or CD34+ precursors, have been

Cytokines

As mentioned previously, different cytokines are required to induce the in vitro differentiation of DCs from different precursors. These cytokine combinations were defined on the basis of differentiation protocols from hematopoietic precursors and complex cytokine-combination tests. Additional information concerning the involvement of cytokines in the differentiation of DCs arises from genetically deficient mice. These experimental data indicate that some cytokines appear to have a dispensable

Conclusions

Current information from humans and mice does not support a conclusive definition of the physiological differentiation pathways that generate DCs in vivo. This controversial situation originates as the consequence of experimental evidence suggesting that the in vivo differentiation of a particular DC subpopulation from a myeloid or lymphoid progenitor might be unrelated to its possible generation under experimental conditions.

In this sense, when analyzing the derivation of mouse DCs by transfer

Acknowledgements

Our studies were funded by the European Commission (grant #QLRT-1999-00276), the Comunidad de Madrid of Spain (grant #08.1/0076/2000) and the Ministerio de Ciencia y Tecnologı́a of Spain (grant #BOS 2000-0558).

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