Plasmacytoid Dendritic Cells and Immunotherapy in Multiple Sclerosis

Felipe von Glehn; Leonilda M Santos; Konstantin E Balashov

Disclosures

Immunotherapy. 2012;4(10):1053-1061. 

In This Article

Abstract and Introduction

Abstract

Plasmacytoid dendritic cells (pDCs) are specialized APCs implicated in the pathogenesis of many human diseases. Compared with other peripheral blood mononuclear cells, pDCs express a high level of TLR9, which recognizes viral DNA at the initial phase of viral infection. Upon stimulation, these cells produce large amounts of type I interferon and other proinflammatory cytokines and are able to prime T lymphocytes. Thus, pDCs regulate innate and adaptive immune responses. This article reviews select aspects of pDC biology relevant to the disease pathogenesis and immunotherapy in multiple sclerosis. Many unresolved questions remain in this area, promising important future discoveries in pDC research.

Introduction

Since the early reference to plasmacytoid dendritic cells (pDCs) in the paracortical area of reactive lymph nodes in 1958 by Lennert and Remmele,[1] an abundance of new information about their important role in the immune system has emerged. The most important milestones in their characterization are:

  • Initial determination of their surface phenotype (CD4+, CD123+ [α-chain of IL-3 receptor] and CD68+);[2,3]

  • Isolation of pDCs from human blood in 1999;[4,5]

  • Identification of BDCA-2 (CD303) and BDCA-4 (neuropilin-1) on pDCs as selective pDC markers;[6,7]

  • Discovery of the murine counterpart in 2001;[8–10]

  • In vitro establishment of derivation of pDCs from human and murine hematopoietic progenitors.[11,12]

pDCs are the major producers of type I interferons and have the unique ability to link innate and adaptive immunity. After microbial stimulation, they can also differentiate into mature pDCs capable of stimulating naive T cells and modulate the adaptive immune response.[13]

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