[In vitro differenciation and functions of dendritic cells obtained from CD34+ hematopoietic progenitors]

Dendritic Cells (DC) are professional antigen presenting cells, necessary during the initiation of immune responses. The study of the role of DC in the establishment of this response has long been tempered by the difficulties to purify DC in sufficient numbers. In vitro generation of DC, from CD34+ hematopoietic progenitors in human and mice, should permit to clarify the relationships between the different DC types isolated in vivo and their roles. GM-CSF has been described to play a key role in the propagation of DC. In human, in association with TNF alpha, it allows the generation of DC from CD34+ progenitors. Those in vitro generated DC are capable of receptor mediated endocytosis and can present soluble antigen to specific T cell clones and activate naive T cells. During activation of naive T cells CD86 (on DC)--CD28 (on T lymphocyte) interaction seems to play a critical role. Interestingly, DC express a functional CD40, which triggering upregulates expression of CD80 and CD86 and induces cytokine production, indicating a reciprocal talk between DC and T cells during the course of antigen presentation. Finally, in vitro generated DC interact directly with B cells, activated through their CD40 antigen, leading to enhanced growth, differentiation (IgM production) and preferential isotype switch towards IgA. Thus, in the extrafollicular area of secondary lymphoid organs, in addition to prime naive T cells, DC might also directly provide costimulatory signals involved during the initiation of primary B cell responses.