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Blood, 15 July 2006, Vol. 108, No. 2, pp. 609-617.
Prepublished online as a Blood First Edition Paper on March 28, 2006; DOI 10.1182/blood-2005-11-4490.
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IMMUNOBIOLOGY
ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells
Fabrizio Mattei,
Giovanna Schiavoni,
Paola Borghi,
Massimo Venditti,
Irene Canini,
Paola Sestili,
Immacolata Pietraforte,
Herbert C. Morse, III,
Carlo Ramoni,
Filippo Belardelli, and
Lucia Gabriele
From the Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; and the Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Interferon consensus sequence-binding protein (ICSBP)/interferon regulatory factor 8 (IRF-8) is a transcription factor that plays critical roles in the differentiation of defined dendritic-cell (DC) populations and in the immune response to many pathogens. In this study, we show that splenic DCs (s-DCs) from ICSBP–/– mice are markedly defective in their ability to capture and to present exogenous antigens (Ags) to naive CD4+ T lymphocytes. We found that CD8 + DCs and, to a lesser extent, CD8– DCs from ICSBP–/– mice are impaired at internalizing Ags, either through a receptor-mediated pathway or by macropinocytosis, in spite of having a more immature phenotype than their wild-type (WT) counterparts. These features reflected a greatly impaired ability of ICSBP–/– s-DCs to present injected soluble ovalbumin (OVA) to OVA-specific CD4+ T cells in vivo. Conversely, bone marrow (BM)–derived DCs from ICSBP–/– mice, in keeping with their immature phenotype, exhibited higher endocytic activity than WT cells. However, Ag-loaded ICSBP–/– BM-DCs were defective in priming Ag-specific CD4+ T lymphocytes and failed to induce a contact hypersensitivity (CHS) response when injected into competent WT hosts. Together, these results indicate that, throughout the developmental program of DCs, ICSBP differentially controls Ag uptake and MHC class II (MHC-II) presentation affecting both functions only in differentiated peripheral DCs.
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