The Journal of Experimental Medicine
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Published 19 August 2002. doi:10.1084/jem.20011608
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© Rockefeller University Press, 0022-1007/2002/8/517/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 4, August 19, 2002 517-527

The CD16+ (Fc{gamma}RIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting

Gwendalyn J. Randolph1, Guzman Sanchez-Schmitz1, Ronald M. Liebman1 and Knut Schäkel2

1 The Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, New York, NY 10029
2 Institute of Immunology, Department of Dermatology, Medical Faculty, Technical University of Dresden, D-01307 Dresden, Germany

Address correspondence to Gwendalyn J. Randolph, Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, 1425 Madison Ave., Box 1496, New York, NY 10029. Phone: 212-659-8262; Fax: 212-803-6740; E-mail: gwendalyn.randolph{at}mssm.edu

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 (Fc{gamma} 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 TGFß1. 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.

Key Words: antigen presentation • cell survival • transforming growth factors • IgG receptors • cell differentiation


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