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*
Division of Dermatology and
Pulmonary Medicine,
Department of Microbiology and Immunology, and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095;
§
Genentech Incorporated, South San Francisco, CA 94080; and
¶
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235
The ability of dendritic cells (DC) to initiate immune responses in
naive T cells is dependent upon a maturation process that allows the
cells to develop their potent Ag-presenting capacity. Although immature
DC can be derived in vitro by treatment of peripheral blood monocytes
with GM-CSF and IL-4, additional signals such as those provided by
TNF-
, CD40 ligand, or LPS are required for complete maturation and
maximum APC function. Because we recently found that microbial
lipoproteins can activate monocytes and DC through Toll-like receptor
(TLR) 2, we also investigated whether lipoproteins can drive DC
maturation. Immature DC were cultured with or without lipoproteins and
were monitored for expression of cell surface markers indicative of
maturation. Stimulation with lipopeptides increased expression of CD83,
MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression
and endocytic activity; these lipopeptide-matured DC also displayed
enhanced T cell stimulatory capacity in MLR, as measured by T cell
proliferation and IFN-
secretion. The lipid moiety of the
lipopeptide was found to be essential for induction of maturation.
Preincubation of maturing DC with an anti-TLR2 blocking Ab before
addition of lipopeptide blocked the phenotypic and functional changes
associated with DC maturation. These results demonstrate that
lipopeptides can stimulate DC maturation via TLR2, providing a
mechanism by which products of bacteria can participate in the
initiation of an immune response.
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K. Tschoep, T. C. Manning, H. Harlin, C. George, M. Johnson, and T. F. Gajewski Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines J. Leukoc. Biol., July 1, 2003; 74(1): 69 - 80. [Abstract] [Full Text] [PDF]
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D. J. Shedlock, J. K. Whitmire, J. Tan, A. S. MacDonald, R. Ahmed, and H. Shen Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection J. Immunol., February 15, 2003; 170(4): 2053 - 2063. [Abstract] [Full Text] [PDF]
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P. A. Sieling, W. Chung, B. T. Duong, P. J. Godowski, and R. L. Modlin Toll-Like Receptor 2 Ligands as Adjuvants for Human Th1 Responses J. Immunol., January 1, 2003; 170(1): 194 - 200. [Abstract] [Full Text] [PDF]
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 K. Bieback, E. Lien, I. M. Klagge, E. Avota, J. Schneider-Schaulies, W. P. Duprex, H. Wagner, C. J. Kirschning, V. ter Meulen, and S. Schneider-Schaulies Hemagglutinin Protein of Wild-Type Measles Virus Activates Toll-Like Receptor 2 Signaling J. Virol., July 29, 2002; 76(17): 8729 - 8736. [Abstract] [Full Text] [PDF]
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A. Ouaissi, E. Guilvard, Y. Delneste, G. Caron, G. Magistrelli, N. Herbault, N. Thieblemont, and P. Jeannin The Trypanosoma cruzi Tc52-Released Protein Induces Human Dendritic Cell Maturation, Signals Via Toll-Like Receptor 2, and Confers Protection Against Lethal Infection J. Immunol., June 15, 2002; 168(12): 6366 - 6374. [Abstract] [Full Text] [PDF]
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 K. Edfeldt, J. Swedenborg, G. K. Hansson, and Z.-q. Yan Expression of Toll-Like Receptors in Human Atherosclerotic Lesions: A Possible Pathway for Plaque Activation Circulation, March 12, 2002; 105(10): 1158 - 1161. [Abstract] [Full Text] [PDF]
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 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
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N. V. Serbina, V. Lazarevic, and J. L. Flynn CD4+ T Cells Are Required for the Development of Cytotoxic CD8+ T Cells During Mycobacterium tuberculosis Infection J. Immunol., December 15, 2001; 167(12): 6991 - 7000. [Abstract] [Full Text] [PDF]
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 N. Kadowaki, S. Ho, S. Antonenko, R. de Waal Malefyt, R. A. Kastelein, F. Bazan, and Y.-J. Liu Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens J. Exp. Med., September 17, 2001; 194(6): 863 - 870. [Abstract] [Full Text] [PDF]
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J. R. Bleharski, K. R. Niazi, P. A. Sieling, G. Cheng, and R. L. Modlin Signaling Lymphocytic Activation Molecule Is Expressed on CD40 Ligand-Activated Dendritic Cells and Directly Augments Production of Inflammatory Cytokines J. Immunol., September 15, 2001; 167(6): 3174 - 3181. [Abstract] [Full Text] [PDF]
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R. T. Semnani, H. Sabzevari, R. Iyer, and T. B. Nutman Filarial Antigens Impair the Function of Human Dendritic Cells during Differentiation Infect. Immun., September 1, 2001; 69(9): 5813 - 5822. [Abstract] [Full Text] [PDF]
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R. A. Silva, T. F. Pais, and R. Appelberg Blocking the Receptor for IL-10 Improves Antimycobacterial Chemotherapy and Vaccination J. Immunol., August 1, 2001; 167(3): 1535 - 1541. [Abstract] [Full Text] [PDF]
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C. Neufert, R. K. Pai, E. H. Noss, M. Berger, W. H. Boom, and C. V. Harding Mycobacterium tuberculosis 19-kDa Lipoprotein Promotes Neutrophil Activation J. Immunol., August 1, 2001; 167(3): 1542 - 1549. [Abstract] [Full Text] [PDF]
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E. H. Noss, R. K. Pai, T. J. Sellati, J. D. Radolf, J. Belisle, D. T. Golenbock, W. H. Boom, and C. V. Harding Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis J. Immunol., July 15, 2001; 167(2): 910 - 918. [Abstract] [Full Text] [PDF]
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