PMID- 20729332 OWN - NLM STAT- MEDLINE DCOM- 20101123 LR - 20230425 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 185 IP - 6 DP - 2010 Sep 15 TI - Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes. PG - 3426-35 LID - 10.4049/jimmunol.1001205 [doi] AB - Dendritic cells (DCs), which maintain tolerance and orchestrate T cell immune responses, comprise a heterogeneous group of cells. For example, in the steady state, murine spleen contains pre-DC-derived CD8(+) and CD8(-) conventional DCs. During inflammation, monocytes become activated and acquire some DC-like features, such as expression of CD11c and MHC class II. Although each of these cell types can present Ag, the relative efficiency of processing and presentation after Ag capture by different routes has not yet been systematically compared. To this end, we administered OVA to various conventional DCs and activated monocytes by receptor-mediated endocytosis, pinocytosis, or phagocytosis and measured internalization and presentation to MHC class I- and MHC class II-restricted T cells. We find that CD8(-) DCs are more efficient than any other type of APC tested in terms of presenting Ag to MHC class II-restricted T cells, irrespective of the route of Ag capture. In contrast, both subsets of splenic DCs are highly effective in cross-presenting Ags to CD8(+) T cells. DCs and activated monocytes cross-presented Ags delivered by DEC205-mediated endocytosis and pinocytosis. However, DCs differ from activated monocytes in that the latter are several orders of magnitude less efficient in presenting Ags captured by phagocytosis to CD8(+) or CD4(+) T cells. We conclude that DCs derived from pre-DCs differ from monocyte-derived cells in that DCs process and present Ags efficiently irrespective of the route of Ag capture. Our observations have significant implications for understanding initiation of immune responses and vaccination strategies targeting DCs and activated monocytes. FAU - Kamphorst, Alice O AU - Kamphorst AO AD - Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. FAU - Guermonprez, Pierre AU - Guermonprez P FAU - Dudziak, Diana AU - Dudziak D FAU - Nussenzweig, Michel C AU - Nussenzweig MC LA - eng GR - HHMI/Howard Hughes Medical Institute/United States GR - P01 AI051573/AI/NIAID NIH HHS/United States GR - AI051573/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100820 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, CD) RN - 0 (CD8 Antigens) RN - 0 (DEC-205 receptor) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Lectins, C-Type) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (Receptors, Cell Surface) SB - IM MH - Animals MH - Antigens, CD/physiology MH - CD8 Antigens/metabolism/*physiology MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cells, Cultured MH - Cross-Priming/*immunology MH - Dendritic Cells/cytology/*immunology/metabolism MH - Endocytosis/immunology MH - Histocompatibility Antigens Class I/immunology/metabolism MH - Histocompatibility Antigens Class II/immunology/metabolism MH - Lectins, C-Type/physiology MH - Macrophage Activation/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Minor Histocompatibility Antigens MH - Monocytes/*immunology/metabolism MH - Receptors, Cell Surface/physiology MH - Resting Phase, Cell Cycle/immunology PMC - PMC3013633 MID - NIHMS256220 OID - NLM: HHMIMS256220 EDAT- 2010/08/24 06:00 MHDA- 2010/12/14 06:00 PMCR- 2011/09/15 CRDT- 2010/08/24 06:00 PHST- 2010/08/24 06:00 [entrez] PHST- 2010/08/24 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] PHST- 2011/09/15 00:00 [pmc-release] AID - jimmunol.1001205 [pii] AID - 10.4049/jimmunol.1001205 [doi] PST - ppublish SO - J Immunol. 2010 Sep 15;185(6):3426-35. doi: 10.4049/jimmunol.1001205. Epub 2010 Aug 20.