PMID- 12391196 OWN - NLM STAT- MEDLINE DCOM- 20021210 LR - 20220311 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 169 IP - 9 DP - 2002 Nov 1 TI - Monocyte chemoattractant protein-1 selectively inhibits the acquisition of CD40 ligand-dependent IL-12-producing capacity of monocyte-derived dendritic cells and modulates Th1 immune response. PG - 4861-6 AB - Accumulating evidence indicates that monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, also displays immunoregulatory functions and may be involved in Th subset differentiation. In this study, we examined the effects of MCP-1 on the cytokine-driven differentiation of monocytes into dendritic cells (DCs), the most potent APCs for naive T cells. We found that DCs generated in the presence of MCP-1 displayed a markedly reduced production of IL-12 in response to CD40 ligand but not in response to Staphylococcus aureus stimulation in the presence or absence of IFN-gamma. The production of IL-10, a potent endogenous IL-12 inhibitor, was not affected by MCP-1. Whereas the inhibitory activity of MCP-1 on IL-12 production by monocytes was sensitive to pertussis toxin, its effects on DC differentiation were pertussis toxin resistant. MCP-1 did not affect the surface phenotype and T cell-stimulating activity of DCs, but most interestingly, naive T cells stimulated with MCP-1-primed DCs produced much less IFN-gamma but the same levels of IL-13. Taken together, our results indicated that MCP-1 modulates the differentiation of monocytes into DCs and may thereby inhibit Th1 cell development. FAU - Omata, Nemuko AU - Omata N AD - Department of Pediatrics, Faculty of Medicine, Fukui Medical University, Japan. FAU - Yasutomi, Motoko AU - Yasutomi M FAU - Yamada, Akiko AU - Yamada A FAU - Iwasaki, Hiromichi AU - Iwasaki H FAU - Mayumi, Mitsufumi AU - Mayumi M FAU - Ohshima, Yusei AU - Ohshima Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adjuvants, Immunologic) RN - 0 (CD40 Antigens) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Immunosuppressive Agents) RN - 0 (Macrophage Inflammatory Proteins) RN - 147205-72-9 (CD40 Ligand) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.4.2.31 (Pertussis Toxin) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - CD40 Antigens/physiology MH - CD40 Ligand/*physiology MH - Cell Differentiation/immunology MH - Cells, Cultured MH - Chemokine CCL2/*pharmacology MH - Chemokine CCL4 MH - Dendritic Cells/cytology/*immunology/metabolism MH - Dose-Response Relationship, Immunologic MH - Down-Regulation/immunology MH - Humans MH - Immunosuppressive Agents/*pharmacology MH - Interferon-gamma/biosynthesis MH - Interleukin-12/*antagonists & inhibitors/*biosynthesis MH - Interphase/immunology MH - Kinetics MH - Macrophage Inflammatory Proteins/pharmacology MH - Monocytes/cytology/*immunology/metabolism MH - Pertussis Toxin/pharmacology MH - Th1 Cells/*immunology/metabolism EDAT- 2002/10/23 04:00 MHDA- 2002/12/11 04:00 CRDT- 2002/10/23 04:00 PHST- 2002/10/23 04:00 [pubmed] PHST- 2002/12/11 04:00 [medline] PHST- 2002/10/23 04:00 [entrez] AID - 10.4049/jimmunol.169.9.4861 [doi] PST - ppublish SO - J Immunol. 2002 Nov 1;169(9):4861-6. doi: 10.4049/jimmunol.169.9.4861.