University of Virginia Health System

Dendritic Cell
(Antigen Presenting Cells)

Lymph node touch imprint, Wright-Giemsa stain, 500x

Description:

Dendritic cells are large, predominently tissue-based cells that morphologically resemble histiocytes (macrophages). They have an abundant blue-grey cytoplasm, often with a ground-glass appearance, and usually long membrane projections. The nucleus is small, round, or oval with coarse evenly dispersed chromatin and a single nucleolous is often present. In the photograph above, the lymphocyte seen in close proximity may be undergoing the process of antigen presentation. Dendritic cells have been designated by different terms depending on their location:

• Follicular dendritic cell (FDC)- germinal center of secondary lymph follicles
• Interdigitating cell (IDC)- the interfollicular (T-cell) zone of lymph nodes and thymus
• Langerhans cell (LC)- epidermis
• Veiled cell (VC)- afferent lymph
• Mucosal dendritic cell- mucosal-associated lymphoid tissue (MALT)

Subsets of dendritic cells have also been identified based on their immunophenotypic profile, conventional dendritic cell (cDC) that are CD123+, and plasmacytoid dendritic cell (pDC) that are CD11c+.

Development, Function and Trafficking:

Dendritic cells are derived from hemopoietic stem cells through either the common lymphoid or the common myeloid progenitor pathways. Precursor dendritic cells are released from the bone marrow into the circulation and exit into the various peripheral tissues and organs, and differentiate into immature dendritic cells (iDCs). Except for monocytes, the precursor dendritic cells cannot be identified morphologically by light microscopy on a peripheral blood smear. They probably reside in the small lymphocyte gate.

The tissue-based iDCs, particularly those in the skin and MALT locations recognize pathogens that enter these areas, and do so through their pattern recognition receptors (PRRs). These receptors recognize various molecules on microorganisms referred to as pathogen-associated molecular patterns (PAMPs) that have been evolutionarily conserved. Once pathogenetic material is engulfed and processed, the iDCs exit through afferent lymphatics to the secondary lymphoid organs. During this migration, iDCs mature and express human leukocyte antigens (HLAs), class I and class II on their surfaces. Antigen presentation to naive lymphocytes, mostly T cells, is mediated by the HLAs. The HLA-I and HLA-II membrane proteins are encoded by genes in the major histocompatability complex (MHC). In general, HLA-I (MHC-I) presents antigen to CD-8 T cells while HLA-II (MHC-II) presents to CD-4 T cells. Antigen presentation can only be accomplished by dendritic cells that are histocompatible with the host. Other cells (e.g. B cells, eosinophils, endothelial cells) also can present antigen to T cells.

Once antigenic stimulation occurs, lymphocytes differentiate to become committed (memory) lymphocytes. These memory lymphocytes then exit the secondary lymphoid organs through efferent lymphatics into large lymphatic channels such as the thoracic duct which empties into the left subclavian vein. They then home to peripheral tissues where the initial pathogen-DC contact occurred. This remarkable property of memory lymphocytes is conferred by dendritic cells (DCs) specific to that particular area.

A subset of dendritic cells referred to as interferon-producing killer dendritic cells (IKDCs) can directly lyse tumor or pathogen-infected cells, and at the same time activate T cells.

General References:

1. Larosa CV, Stadtfeld M, Graf T. Determinant of lymphoid-myeloid lineage diversification. Annu Rev Immunal 2006; 24:705-38
2. Blom B, Spits H. Development of human lymphoid cells. Annu Rev Immunal 2006; 24:287-320
3. Taieb J, Chaput N, Menard C, et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 2006; 12:214-9

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