The CD16+ (FcγRIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting

Much remains to be learned about the physiologic events that promote monocytes to become lymph-homing dendritic cells (DCs). In a model of transendothelial trafficking, some monocytes become DCs in response to endogenous signals. These DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse transmigration), reminiscent of the migration into lymphatic vessels. Here we show that the subpopulation of monocytes that expresses CD16 (Fcγ receptor III) is predisposed to become migratory DCs. The vast majority of cells derived from CD16+ monocytes reverse transmigrated, and their presence was associated with migratory cells expressing high levels of CD86 and human histocompatibility leukocyte antigen (HLA)-DR, and robust capacity to induce allogeneic T cell proliferation. A minority of CD16− monocytes reverse transmigrated, and these cells stimulated T cell proliferation less efficiently. CD16 was not functionally required for reverse transmigration, but promoted cell survival when yeast particles (zymosan) were present as a maturation stimulus in the subendothelial matrix. The cell surface phenotype and migratory characteristics of CD16+ monocytes were inducible in CD16− monocytes by preincubation with TGFβ1. We propose that CD16+ monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels.

[1]  David M. Mosser,et al.  Cutting Edge: Biasing Immune Responses by Directing Antigen to Macrophage Fcγ Receptors1 , 2002, The Journal of Immunology.

[2]  Giovanni Melioli,et al.  Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK Cells , 2002, The Journal of experimental medicine.

[3]  S. Amigorena,et al.  Fcγ Receptors and Cross-Presentation in Dendritic Cells , 2002, The Journal of experimental medicine.

[4]  C. Bogdan,et al.  Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity , 2002, The Journal of experimental medicine.

[5]  G. Sanchez-Schmitz,et al.  CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. , 2001, International immunology.

[6]  G. Randolph Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. , 2001, Seminars in immunology.

[7]  C. Mold,et al.  Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis1 , 2001, The Journal of Immunology.

[8]  S. Nishikawa,et al.  Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells. , 2001, International immunology.

[9]  Tong-Yuan Yang,et al.  Aberrant in Vivo T Helper Type 2 Cell Response and Impaired Eosinophil Recruitment in Cc Chemokine Receptor 8 Knockout Mice , 2001, The Journal of experimental medicine.

[10]  A. S. Dagtas,et al.  Interleukin‐10 induces macrophage apoptosis and expression of CD16 (FcγRIII) whose engagement blocks the cell death programme and facilitates differentiation , 2001, Immunology.

[11]  M. Ernst,et al.  Identification of a novel dendritic cell‐like subset of CD64+ / CD16+ blood monocytes , 2001, European journal of immunology.

[12]  A. Aderem,et al.  The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[13]  I. Maridonneau-Parini,et al.  Nonopsonic Phagocytosis of Zymosan and Mycobacterium kansasii by CR3 (CD11b/CD18) Involves Distinct Molecular Determinants and Is or Is Not Coupled with NADPH Oxidase Activation , 2000, Infection and Immunity.

[14]  L. Weiss,et al.  CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit phenotypic and functional dendritic cell‐like characteristics , 2000, European journal of immunology.

[15]  T. Di Pucchio,et al.  Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice , 2000, The Journal of experimental medicine.

[16]  M. Frankenberger,et al.  The M-DC8-positive leukocytes are a subpopulation of the CD14+ CD16+ monocytes. , 2000, Immunobiology.

[17]  S. Gartner HIV Infection and Dementia , 2000, Science.

[18]  N. Kadowaki,et al.  The nature of the principal type 1 interferon-producing cells in human blood. , 1999, Science.

[19]  W. Nockher,et al.  CD 14++ Monocytes, CD14+/CD16+ Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy , 1999, Clinical chemistry and laboratory medicine.

[20]  K. Schäkel,et al.  A novel dendritic cell population in human blood: one‐step immunomagnetic isolation by a specific mAb (M‐DC8) and in vitro priming of cytotoxic T lymphocytes , 1998, European journal of immunology.

[21]  R. Steinman,et al.  Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. , 1998, Science.

[22]  R. Steinman,et al.  A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G. Fingerle-Rowson,et al.  Selective depletion of CD14+ CD16+ monocytes by glucocorticoid therapy , 1998, Clinical and experimental immunology.

[24]  M. McGrath,et al.  Unique monocyte subset in patients with AIDS dementia , 1997, The Lancet.

[25]  J. Letterio,et al.  A Role for Endogenous Transforming Growth Factor β1 in Langerhans Cell Biology:  The Skin of   Transforming Growth Factor β1 Null Mice Is Devoid of  Epidermal Langerhans Cells , 1996, The Journal of experimental medicine.

[26]  M. Brook,et al.  Novel polymer‐grafted starch microparticles for mucosal delivery of vaccines , 1996, Immunology.

[27]  Liangji Zhou,et al.  CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  W. Muller,et al.  Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural killer cell transendothelial migration and beta 2 integrin activation. , 1996, Journal of immunology.

[29]  G. Randolph,et al.  Mononuclear phagocytes egress from an in vitro model of the vascular wall by migrating across endothelium in the basal to apical direction: role of intercellular adhesion molecule 1 and the CD11/CD18 integrins , 1996, The Journal of experimental medicine.

[30]  H. Ziegler-Heitbrock,et al.  Interleukin-10 drives human monocytes to CD16 positive macrophages. , 1996, Journal of inflammation.

[31]  J. Ceuppens,et al.  Granulocyte-macrophage colony-stimulating factor antagonizes the transforming growth factor-beta-induced expression of Fc gamma RIII (CD16) on human monocytes. , 1996, Immunology.

[32]  C. Estcourt,et al.  CD14lowCD16high: A cytokine‐producing monocyte subset which expands during human immunodeficiency virus infection , 1995, European journal of immunology.

[33]  P. Allavena,et al.  IL-13 supports differentiation of dendritic cells from circulating precursors in concert with GM-CSF. , 1995, European cytokine network.

[34]  E. Jacobs,et al.  Alterations in phenotype and cell-surface antigen expression levels of human monocytes: differential response to in vivo administration of rhM-CSF or rhGM-CSF. , 1995, Cytometry.

[35]  L. Minasian,et al.  CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor. , 1995, Blood.

[36]  P. Lipsky,et al.  Human peripheral blood dendritic cell subsets. Isolation and characterization of precursor and mature antigen-presenting cells. , 1994, Journal of immunology.

[37]  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.

[38]  M. Furie,et al.  Monocytes use either CD11/CD18 or VLA-4 to migrate across human endothelium in vitro. , 1994, Journal of immunology.

[39]  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.

[40]  L. Davis,et al.  Isolation and characterization of human peripheral blood dendritic cells. , 1993, Journal of immunology.

[41]  H. Schuurman,et al.  Tissue distribution of human IgG Fc receptors CD16, CD32 and CD64: An immunohistochemical study , 1993, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[42]  W. Muller,et al.  Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay , 1992, The Journal of experimental medicine.

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

[44]  B. Passlick,et al.  Identification and characterization of a novel monocyte subpopulation in human peripheral blood. , 1989, Blood.

[45]  S. Clarkson,et al.  CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes , 1988, The Journal of experimental medicine.

[46]  R. van Furth,et al.  THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES , 1968, The Journal of experimental medicine.