Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34+ hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony–stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-α or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34+ HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3α, but also to MIP-1α and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-α, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3β. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3α and MIP-3β, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3β responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3β is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3α mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3β mRNA specifically in T cell–rich areas, suggests a role for MIP-3α/CCR6 in recruitment of immature DCs at site of injury and for MIP-3β/CCR7 in accumulation of antigen-loaded mature DCs in T cell–rich areas.

[1]  T. Springer,et al.  B Lymphocyte Chemotaxis Regulated in Association with Microanatomic Localization, Differentiation State, and B Cell Receptor Engagement , 1998, The Journal of experimental medicine.

[2]  R. Steinman,et al.  Mature Dendritic Cells Respond to SDF-1, but not to Several β-Chemokines , 1998 .

[3]  H. Broxmeyer,et al.  CKβ-11/Macrophage Inflammatory Protein-3β/EBI1-Ligand Chemokine Is an Efficacious Chemoattractant for T and B Cells , 1998, The Journal of Immunology.

[4]  C Caux,et al.  The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. , 1998, Journal of immunology.

[5]  E. Butcher,et al.  Chemokines and the arrest of lymphocytes rolling under flow conditions. , 1998, Science.

[6]  J. Banchereau,et al.  Isolation and propagation of human dendritic cells , 1998 .

[7]  J. White,et al.  CK beta-11/macrophage inflammatory protein-3 beta/EBI1-ligand chemokine is an efficacious chemoattractant for T and B cells. , 1998, Journal of immunology.

[8]  R. Steinman,et al.  Mature dendritic cells respond to SDF-1, but not to several beta-chemokines. , 1998, Immunobiology.

[9]  T. Mcclanahan,et al.  CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3α and Is Highly Expressed in Human Dendritic Cells , 1997, The Journal of experimental medicine.

[10]  A. Mantovani,et al.  Cloning and Characterization of a Specific Receptor for the Novel CC Chemokine MIP-3α from Lung Dendritic Cells , 1997, The Journal of experimental medicine.

[11]  Antonio Lanzavecchia,et al.  Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells , 1997, Nature.

[12]  M. Gobbi,et al.  Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. , 1997, Journal of immunology.

[13]  C Caux,et al.  CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis. , 1997, Blood.

[14]  S. Ullrich,et al.  STRL22 is a receptor for the CC chemokine MIP-3alpha. , 1997, Biochemical and biophysical research communications.

[15]  T. Mcclanahan,et al.  A dendritic-cell-derived C–C chemokine that preferentially attracts naive T cells , 1997, Nature.

[16]  H. Nomiyama,et al.  Identification of CCR6, the Specific Receptor for a Novel Lymphocyte-directed CC Chemokine LARC* , 1997, The Journal of Biological Chemistry.

[17]  H. Nomiyama,et al.  Molecular Cloning of a Novel Human CC Chemokine EBI1-ligand Chemokine That Is a Specific Functional Ligand for EBI1, CCR7* , 1997, The Journal of Biological Chemistry.

[18]  P. Allavena,et al.  Human Macrophage–derived Chemokine (mdc), a Novel Chemoattractant for Monocytes, Monocyte-derived Dendritic Cells, and Natural Killer Cells , 1997 .

[19]  M. Klemsz,et al.  Cloning and Characterization of Exodus, a Novel β-Chemokine , 1997 .

[20]  P. Allavena,et al.  IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences. , 1997, Journal of immunology.

[21]  C. Mackay,et al.  The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Sica,et al.  Bacterial Lipopolysaccharide Rapidly Inhibits Expression of C–C Chemokine Receptors in Human Monocytes , 1997, The Journal of experimental medicine.

[23]  T. Mcclanahan,et al.  Identification through bioinformatics of two new macrophage proinflammatory human chemokines: MIP-3alpha and MIP-3beta. , 1997, Journal of immunology.

[24]  F. Sallusto,et al.  Origin, maturation and antigen presenting function of dendritic cells. , 1997, Current opinion in immunology.

[25]  M. Klemsz,et al.  Cloning and characterization of exodus, a novel beta-chemokine. , 1997, Blood.

[26]  R. Testi,et al.  Ceramide Inhibits Antigen Uptake and Presentation by Dendritic Cells , 1996, The Journal of experimental medicine.

[27]  J. Banchereau,et al.  Dendritic cells capable of stimulating T cells in germinal centres , 1996, Nature.

[28]  B. Premack,et al.  Chemokine receptors: Gateways to inflammation and infection , 1996, Nature Medicine.

[29]  P. De Baetselier,et al.  Regulation of Dendritic Cell Numbers and Maturation by Lipopolysaccharide in Vivo , 1996 .

[30]  W. Gong,et al.  Human recombinant monocyte chemotactic protein and other c‐c chemokines bind and induce directional migration of dendritic cells in vitro , 1996, Journal of leukocyte biology.

[31]  M. Baggiolini,et al.  Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes , 1996, The Journal of experimental medicine.

[32]  J. Banchereau,et al.  CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha , 1996, The Journal of experimental medicine.

[33]  D. Strunk,et al.  Generation of human dendritic cells/Langerhans cells from circulating CD34+ hematopoietic progenitor cells. , 1996, Blood.

[34]  J. Banchereau,et al.  Fas ligation induces apoptosis of CD40-activated human B lymphocytes , 1995, The Journal of experimental medicine.

[35]  P. Allavena,et al.  Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. , 1995, Journal of immunology.

[36]  C Danieli,et al.  Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products , 1995, The Journal of experimental medicine.

[37]  P. Morris,et al.  Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1 , 1995, The Journal of experimental medicine.

[38]  C. Edwards,et al.  Endotoxin-mediated dendritic cell release from the intestine. Characterization of released dendritic cells and TNF dependence. , 1995, Journal of immunology.

[39]  I. Kimber,et al.  Tumour necrosis factor-alpha is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization. , 1995, Immunology.

[40]  T. Schall,et al.  Chemokines, leukocyte trafficking, and inflammation. , 1994, Current opinion in immunology.

[41]  J. Banchereau,et al.  B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells , 1994, The Journal of experimental medicine.

[42]  R. Steinman,et al.  The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro , 1994, The Journal of experimental medicine.

[43]  R. Eddy,et al.  Cloning of human and mouse EBI1, a lymphoid-specific G-protein-coupled receptor encoded on human chromosome 17q12-q21.2. , 1994, Genomics.

[44]  J. Banchereau,et al.  Activation of human dendritic cells through CD40 cross-linking , 1994, The Journal of experimental medicine.

[45]  First,et al.  Induction of G protein-coupled peptide receptor EBI 1 by human herpesvirus 6 and 7 infection in CD4+ T cells , 1994, Journal of virology.

[46]  F. Sallusto,et al.  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 , 1994, The Journal of experimental medicine.

[47]  P. Holt,et al.  Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces , 1994, The Journal of experimental medicine.

[48]  B. Dewald,et al.  Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. , 1994, Advances in immunology.

[49]  P. Murphy.  The molecular biology of leukocyte chemoattractant receptors. , 1994, Annual review of immunology.

[50]  R. Steinman,et al.  Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium , 1993, The Journal of experimental medicine.

[51]  G. Macpherson,et al.  Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo , 1993, The Journal of experimental medicine.

[52]  E. Kieff,et al.  Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors , 1993, Journal of virology.

[53]  J. Oppenheim.  Overview of chemokines. , 1993, Advances in experimental medicine and biology.

[54]  J. Banchereau,et al.  GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells , 1992, Nature.

[55]  P. Linsley,et al.  Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations , 1992, The Journal of experimental medicine.

[56]  G. Kaplan,et al.  Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing , 1992, The Journal of experimental medicine.

[57]  I. Kimber,et al.  Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans' cell migration. , 1992, Immunology.

[58]  M. Moser,et al.  Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo , 1992, The Journal of experimental medicine.

[59]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.

[60]  C. Bucana,et al.  Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization. , 1990, Journal of immunology.

[61]  R. Steinman,et al.  Migration and maturation of Langerhans cells in skin transplants and explants , 1990, The Journal of experimental medicine.

[62]  R. Steinman,et al.  Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain , 1990, The Journal of experimental medicine.

[63]  A. Demidem,et al.  Functional Dichotomy between Langerhans Cells that Present Antigen to Naive and to Memory/Effector T Lymphocytes , 1990, Immunological reviews.

[64]  R. Steinman,et al.  Dendritic cells pulsed with protein antigens in vitro can prime antigen- specific, MHC-restricted T cells in situ [published erratum appears in J Exp Med 1990 Oct 1;172(4):1275] , 1990, The Journal of experimental medicine.

[65]  J. Banchereau,et al.  Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells. , 1990, Blood.

[66]  M. Peuchmaur,et al.  IL-2 mRNA expression in Tac-positive malignant lymphomas. , 1990, The American journal of pathology.

[67]  P. Peters,et al.  Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. , 1990, The Journal of investigative dermatology.

[68]  J. Streilein,et al.  In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. , 1989, Journal of immunology.

[69]  O. Majdic,et al.  Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. , 1989, The Journal of investigative dermatology.

[70]  R. Steinman,et al.  Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells , 1989, The Journal of experimental medicine.

[71]  P. Woollard,et al.  Contrasting in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12‐hydroxy‐5,8,10,14‐eicosatetraenoic acid , 1988, British journal of pharmacology.

[72]  G. Schuler,et al.  Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells , 1988, The Journal of experimental medicine.

[73]  P. Morris,et al.  Migration patterns of dendritic cells in the mouse. Homing to T cell- dependent areas of spleen, and binding within marginal zone , 1988, The Journal of experimental medicine.

[74]  P. Morris,et al.  Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues , 1988, The Journal of experimental medicine.

[75]  S. Fossum.  Lymph‐Borne Dendritic Leucocytes do Not Recirculate, but Enter the Lymph Node Paracortex to Become Interdigitating Cells , 1988, Scandinavian journal of immunology.

[76]  P. Morris,et al.  Migration patterns of dendritic cells in the mouse. , 1988, Advances in experimental medicine and biology.

[77]  S. Knight,et al.  Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies , 1987, The Journal of experimental medicine.

[78]  R. Steinman,et al.  Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes , 1986, The Journal of experimental medicine.

[79]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[80]  R. Steinman,et al.  Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro , 1985, The Journal of experimental medicine.