PMID- 16423045 OWN - NLM STAT- MEDLINE DCOM- 20060206 LR - 20181113 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 117 IP - 1 DP - 2006 Jan TI - The delivery of an antigen from the endocytic compartment into the cytosol for cross-presentation is restricted to early immature dendritic cells. PG - 97-107 AB - Dendritic cells (DCs) are the only antigen-presenting cell population having a cross-presentation capacity. For cross-presentation, however, the intracellular antigen-processing pathway and its regulatory mechanism have not been defined. Here we report the differences in cross-presentation ability among murine bone marrow-derived immature DC, early immature day8-DC and late immature day10-DC, and fully mature day10 + lipopolysaccharide DC. Day8-DCs and day10-DCs show an immature phenotypic profile but are different in morphology. Day8-DCs can internalize an abundant volume of exogenous soluble ovalbumin (OVA) and result in cross-presentation. In contrast, day10-DCs are not able to cross-present, although they maintain efficient macropinocytosis. Exogenously internalized OVA antigens are stored in the endocytic compartments. The endocytic compartments are temporarily maintained at mildly acidic pH in day8-DCs and are rapidly acidified in day10-DCs after uptake of antigens. We show that OVA antigens accumulated in the endocytic compartments move into the cytosol in day8-DCs but do not in day10-DCs. NH(4)Cl-treatment, which neutralizes the acidic endocytic compartments and/or delays endosomal maturation, restores day10-DCs for transport the stored OVA antigens from the endocytic compartments into the cytosol. Diphenyleneiodonium chloride-treatment, which acidifies the endocytic compartments, decreases an amount of transported OVA antigen into the cytosol in day8-DCs. These data indicate that only the early immature stage of DC interferes with endosomal maturation, even after uptake of exogenous antigens, and then transports the antigens into the cytosol. FAU - Hotta, Chie AU - Hotta C AD - Department of Immunology, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Fujimaki, Haruka AU - Fujimaki H FAU - Yoshinari, Masahiro AU - Yoshinari M FAU - Nakazawa, Masatoshi AU - Nakazawa M FAU - Minami, Mutsuhiko AU - Minami M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 01Q9PC255D (Ammonium Chloride) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Ammonium Chloride/pharmacology MH - Animals MH - *Antigen Presentation MH - Antigens/immunology/metabolism MH - Biological Transport/drug effects/immunology MH - Cell Differentiation/immunology MH - Cross-Priming/drug effects/*immunology MH - Cytosol/immunology MH - Dendritic Cells/drug effects/*immunology MH - Histocompatibility Antigens Class I/immunology MH - Hydrogen-Ion Concentration MH - Mice MH - Mice, Inbred C57BL MH - Ovalbumin/immunology/pharmacokinetics MH - Transport Vesicles/immunology PMC - PMC1782205 EDAT- 2006/01/21 09:00 MHDA- 2006/02/07 09:00 PMCR- 2007/01/01 CRDT- 2006/01/21 09:00 PHST- 2006/01/21 09:00 [pubmed] PHST- 2006/02/07 09:00 [medline] PHST- 2006/01/21 09:00 [entrez] PHST- 2007/01/01 00:00 [pmc-release] AID - IMM2270 [pii] AID - 10.1111/j.1365-2567.2005.02270.x [doi] PST - ppublish SO - Immunology. 2006 Jan;117(1):97-107. doi: 10.1111/j.1365-2567.2005.02270.x.