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RESEARCH PRODUCT

How do dendritic cells prevent autoimmunity: what is a mature dendritic cell in the mouse?

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We appreciate the comment by Morel and Feili-Hariri with regard to our most-recent publication in Trends in Immunology 1xDendritic cells as a tool to induce anergic and regulatory T cells. Jonuleit, H. et al. Trends Immunol. 2001; 7: 394–400Abstract | Full Text | Full Text PDF | Scopus (384)See all References1. We certainly do not argue that other subtypes of dendritic cell (DC) might not be suitable for the induction of tolerance also, but certain experimental differences should be considered, particularly with regard to the maturational status of the murine DCs used by Feili-Hariri et al. 2xImmunotherapy of NOD mice with bone-marrow-derived dendritic cells. Feili-Hariri, M. et al. Diabetes. 1999; 48: 2300–2308Crossref | PubMedSee all References, 3xPhenotypic and functional characteristics of BM-derived DCs from NOD and nondiabetes-prone strains. Feili-Hariri, M. et al. Clin. Immunol. 2001; 98: 133–142Crossref | PubMed | Scopus (67)See all ReferencesAll of the studies mentioned by Morel and Feili-Hariri involve murine autoimmune models using bone-marrow-derived DCs that have been cultured in the presence of granulocyte–macrophage colony-stimulating factor (GM-CSF) – ‘immature’ DCs – or GM-CSF plus interleukin-4 (IL-4) – ‘mature’ DCs. Murine cultures (derived from bone-marrow stem cells) are much more heterogeneous than human cultures of DCs derived from CD14? monocytes and the cells in the two types of culture are not identical. Indeed, it is questionable whether the maturational status of the cultures is comparable. Furthermore, as demonstrated in many murine and human studies, mature DCs normally induce the development of very efficient interferon-γ-producing T cells and their polarization into T helper 1 cells in vitro and in vivo. Therefore, it should be noted that Feili-Hariri et al. 2xImmunotherapy of NOD mice with bone-marrow-derived dendritic cells. Feili-Hariri, M. et al. Diabetes. 1999; 48: 2300–2308Crossref | PubMedSee all References, 3xPhenotypic and functional characteristics of BM-derived DCs from NOD and nondiabetes-prone strains. Feili-Hariri, M. et al. Clin. Immunol. 2001; 98: 133–142Crossref | PubMed | Scopus (67)See all References use artificial autoimmune models for their studies which might not reflect a typical T-cell response to mature DCs (in a ‘real’ autoimmune disease).We would also like to clarify a misunderstanding regarding the regulatory T cells described in the last paragraph of the letter by Morel and Feili-Hariri. Immature DCs do not induce regulatory T1 (Treg1) cells, but regulatory, CD4?CD25? cytotoxic T-lymphocyte antigen 4? T cells, which do not act by releasing IL-10, but by a contact-dependent mechanism. Treg1 cells, as described by Roncarolo et al.4xA CD4? T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Groux, H. et al. Nature. 1997; 389: 737–742Crossref | PubMed | Scopus (2757)See all References4, clearly, are distinct from these cells. Furthermore, mature DCs are not able to induce the development of these CD4?CD25? Treg cells.