Journal of Experimental Medicine, Vol 179, 1109-1118, Copyright © 1994 by Rockefeller University Press

ARTICLES

Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha

F Sallusto and A Lanzavecchia
Basel Institute for Immunology, Switzerland.

Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.
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• Pizzirani, C., Ferrari, D., Chiozzi, P., Adinolfi, E., Sandona, D., Savaglio, E., Di Virgilio, F. (2007). Stimulation of P2 receptors causes release of IL-1{beta}-loaded microvesicles from human dendritic cells. Blood 109: 3856-3864 [Abstract] [Full Text]  
• Paczesny, S., Li, Y.-P., Li, N., Latger-Cannard, V., Marchal, L., Ou-Yang, J.-P., Bordigoni, P., Stoltz, J.-F., Eljaafari, A. (2007). Efficient generation of CD34+ progenitor-derived dendritic cells from G-CSF-mobilized peripheral mononuclear cells does not require hematopoietic stem cell enrichment. J. Leukoc. Biol. 81: 957-967 [Abstract] [Full Text]  
• Fernando, K., Hu, H., Ni, H., Hoxie, J. A., Weissman, D. (2007). Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses. Blood 109: 2538-2544 [Abstract] [Full Text]  
• Ito, Y., Demachi-Okamura, A., Ohta, R., Akatsuka, Y., Nishida, K., Tsujimura, K., Morishima, Y., Takahashi, T., Kuzushima, K. (2007). Full-length EBNA1 mRNA-transduced dendritic cells stimulate cytotoxic T lymphocytes recognizing a novel HLA-Cw*0303- and -Cw*0304-restricted epitope on EBNA1-expressing cells. J. Gen. Virol. 88: 770-780 [Abstract] [Full Text]  
• Cameron, P. U., Handley, A. J., Baylis, D. C., Solomon, A. E., Bernard, N., Purcell, D. F. J., Lewin, S. R. (2007). Preferential Infection of Dendritic Cells during Human Immunodeficiency Virus Type 1 Infection of Blood Leukocytes. J. Virol. 81: 2297-2306 [Abstract] [Full Text]  
• Draghi, M., Pashine, A., Sanjanwala, B., Gendzekhadze, K., Cantoni, C., Cosman, D., Moretta, A., Valiante, N. M., Parham, P. (2007). NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection. J. Immunol. 178: 2688-2698 [Abstract] [Full Text]  
• van Montfort, T., Nabatov, A. A., Geijtenbeek, T. B. H., Pollakis, G., Paxton, W. A. (2007). Efficient Capture of Antibody Neutralized HIV-1 by Cells Expressing DC-SIGN and Transfer to CD4+ T Lymphocytes. J. Immunol. 178: 3177-3185 [Abstract] [Full Text]  
• Landsman, L., Varol, C., Jung, S. (2007). Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung. J. Immunol. 178: 2000-2007 [Abstract] [Full Text]  
• Stopak, K. S., Chiu, Y.-L., Kropp, J., Grant, R. M., Greene, W. C. (2007). Distinct Patterns of Cytokine Regulation of APOBEC3G Expression and Activity in Primary Lymphocytes, Macrophages, and Dendritic Cells. J. Biol. Chem. 282: 3539-3546 [Abstract] [Full Text]  
• Leclerc, D., Beauseigle, D., Denis, J., Morin, H., Pare, C., Lamarre, A., Lapointe, R. (2007). Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells. J. Virol. 81: 1319-1326 [Abstract] [Full Text]  
• Mehrotra, S., Chhabra, A., Hegde, U., Chakraborty, N. G., Mukherji, B. (2007). Inhibition of c-Jun N-terminal kinase rescues influenza epitope-specific human cytolytic T lymphocytes from activation-induced cell death. J. Leukoc. Biol. 81: 539-547 [Abstract] [Full Text]  
• Di Nardo, A., Braff, M. H., Taylor, K. R., Na, C., Granstein, R. D., McInturff, J. E., Krutzik, S., Modlin, R. L., Gallo, R. L. (2007). Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization. J. Immunol. 178: 1829-1834 [Abstract] [Full Text]  
• Gogolak, P., Rethi, B., Szatmari, I., Lanyi, A., Dezso, B., Nagy, L., Rajnavolgyi, E. (2007). Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPAR{gamma}. Blood 109: 643-652 [Abstract] [Full Text]  
• Trinchieri, G. (2007). The Birth of a Cell Type. J. Immunol. 178: 3-4 [Full Text]  
• Thurnher, M. (2007). Lipids in dendritic cell biology: messengers, effectors, and antigens. J. Leukoc. Biol. 81: 154-160 [Abstract] [Full Text]  
• Assier, E., Marin-Esteban, V., Haziot, A., Maggi, E., Charron, D., Mooney, N. (2007). TLR7/8 agonists impair monocyte-derived dendritic cell differentiation and maturation. J. Leukoc. Biol. 81: 221-228 [Abstract] [Full Text]  
• Liu, Y., Gao, X., Masuda, E., Redecha, P. B., Blank, M. C., Pricop, L. (2006). Regulated Expression of Fc{gamma}R in Human Dendritic Cells Controls Cross-Presentation of Antigen-Antibody Complexes. J. Immunol. 177: 8440-8447 [Abstract] [Full Text]  

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