Dendritic Cells

Biology and Clinical Applications

Michael T. Lotze, Angus W. Thomson

• Publisher: Academic Press
• Year: 2001
• ISBN:
  9780080491073
• Edition: 2
• Topic: Ciencias biológicas
• Subtopic: Biología molecular

Dendritic Cells, Second Edition is the new edition of the extremely successful book published in 1998. With the volume of literature on dendritic cells doubling every year, it is almost impossible to keep up. This book provides the most up-to-date synthesis of the literature, written by the very best authors. It is essential reading for any scientist working in immunology, cell biology, infectious diseases, cancer, transplantation, genetic engineering, or the pharmaceutical/biotechnology industry.

An entirely new section on DC biology is included in this edition. Also new to this edition are chapters on:

• Imaging
• Interaction of dendritic cells with viruses
• Dendritic cells and dendrikines, chemokines and the endothelium
• Molecules expressed in dendritic cells
• Role of dendritic cells in wound healing and atherosclerosis
• Delivery of apoptotic bodies
• Genetic engineering of dendritic cells
• Imaging
• Practical aspects of clinical protocol development

I

ORIGIN AND MOLECULAR BIOLOGY OF DENDRITIC CELLS

CHAPTER 1

The development of dendritic cells from hematopoietic precursors

Li Wu¹ and Anne Galy², ¹The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; ²Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA

Experience is not what happens to a man. It is what a man does with what happens to him.

Aldous Huxley

INTRODUCTION

Blood cells are diverse types of cells that provide highly specialized functions such as tissue oxygenation, tissue repair, blood clotting or immune responses. The continuous demand for the supply of these various types of blood cells is provided by the proficient, yet tightly regulated development of hematopoietic progenitor cells. Cell fate specification of these uncommitted multipotential cells is therefore an important aspect of hematopoietic cell development, but one that remains incompletely understood. The study of the dendritic cell (DC) lineage specification has provided interesting insights into this area. DCs constitute a system of hematopoietic cells that are rare but ubiquitously distributed. Several DC types with different biological features have been identified in different tissues, including Langerhans cells (LCs) in the epidermis, interstitial DCs in various tissues, thymic DCs and DC populations found in other lymphoid organs. DCs have powerful functions in the immune system. They can capture and process antigens, then present the antigenic peptides and activate specific T cells (Steinman, 1991; Banchereau and Steinman, 1998).

Variations among the tissue distribution of DCs and differences in their phenotype and function indicate the existence of heterogeneous populations of DCs (Hart, 1997). DCs were originally considered to be of myeloid origin and closely related to monocytes, macrophages and granulocytes. However, recent studies suggested that DCs can be generated along distinct developmental pathways and can originate from precursors of different hematopoietic lineages, with at least two DC lineages being identified so far, namely the conventional myeloid-related DC and the newly defined lymphoid-related DC lineages. Because various populations of DCs in mice (Kronin et al., 1996; Maldonado-Lopez et al., 1999; Pulendran et al., 1999) or humans (Caux et al., 1997) are able to induce distinct types of immune responses, it becomes important to determine the role of their origin in determining functional heterogeneity. An important question is how this heterogeneity arises at the developmental level.

EARLY DEVELOPMENTAL DECISION CHECKPOINTS IN THE HEMATOPOIETIC DEVELOPMENT OF DCs

The early developmental steps of DC formation from hematopoietic progenitor cells are not uniform and involve different types of progenitor cells, different developmental pathways and different signals. Understanding these early events is facilitated by the identification of early developmental checkpoints in the hematopoietic development of DCs.

Early hematopoietic progenitors

The existence and identification of lineage-restricted progenitor cells has been helpful in our understanding of hematopoietic cell fate specification. Multipotent yet lineage-restricted progenitor cells identified and characterized in mice and in humans can be distinguished from the most primitive hematopoietic stem cells (HSCs) based on differences in cell surface phenotype and the capacity and durability of multilineage engraftment. In the murine thymus an early lymphoid-restricted precursor population termed the ‘low CD4 precursor’ has been identified. This precursor population does not express hematopoietic lineage markers (Lin), but expresses low levels of CD4 and Thy-1 and high levels of the hematopoietic progenitor cell markers c-kit and Sca-1 (Wu et al., 1991a). These precursors, although isolated from thymus, are not yet committed to the T-cell lineage and are able to produce T cells, B cells, natural killer (NK) cells and DCs (Wu et al., 1991b; Ardavin et al., 1993). However, they have no myeloid and erythroid differentiation potential (Wu et al., 1991b).

In murine bone marrow (BM), clonogenic common lymphoid and common myeloid progenitors have also been identified recently (Kondo et al., 1997; Akashi et al., 2000). IL-7Rα expression is a main marker to distinguish these two progenitors. The common lymphoid progenitors (CLPs) are Lin⁻, IL⁻7Rα⁺, c-kit^lo and Sca-1^lo. Such cells can generate all lymphoid cells at clonal level and some DCs (Wu et al., unpublished), but not detectable myeloid or erythroid cells (Kondo et al., 1997). The common myeloid progenitors (CMPs) are Lin⁻, IL-7Rα⁻, c-kit⁺, Sca-1⁻, CD34⁺, FcγR^lo (Akashi et al., 2000). These cells can give rise to precursors for megakaryocytes/erythrocytes (MEPs) and precursors for granulocytes/macrophages (GMPs) (Akashi et al., 2000). CMPs also produce DCs (Traver et al., 2000)

The human equivalent of mouse CMPs has not yet been described. However, progenitor cells with features similar to those of the CLPs in mouse have been identified in human. The human BM progenitor cells expressing CD34, CD45RA, CD10 and IL-7Rα, but no lineage-associated markers, have differentiation potential restricted to the production of lymphocytes and DCs, but not of myeloid cells and erythrocytes (Galy et al., 1995b; Ryan et al., 1997). This CLP arises from a myeloid/lymphoid-restricted progenitor cell with limited erythroid differentiation potential that is contained in the CD34⁺CD45RA⁺ cell population (Galy et al., 1995a). Thus, hematopoietic cell fate specification occurs incrementally. The existence ofprogenitor cells that can give rise to several lineages but not to all hematopoietic lineages represents possible developmental checkpoints of hematopoietic differentiation.

Developmental relationships of myeloid lineage and DCs

It is generally assumed that DCs have a ‘myeloid’ origin because they arise from hematopoietic progenitor cells with myeloid differentiation potential and they can be produced from monocytes, a typical myeloid cell. Monocytes can generate immunostimulatory DCs. This differentiation process occurs without proliferation and is induced at a high frequency in culture by granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4 (Romani et al., 1994; Sallusto and Lanzavecchia, 1994; Zhou and Tedder, 1996). In spite of this relat...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Foreword to the Second Edition
• Preface to the Second Edition
• Preface to the First Edition
• PART I: ORIGIN AND MOLECULAR BIOLOGY OF DENDRITIC CELLS
• PART II: DENDRITIC CELL BIOLOGY
• PART III: DENDRITIC CELLS AND INTERACTION WITH OTHER CELLS
• PART IV: DENDRITIC CELLS IN THE PERIPHERY
• PART V: DENDRITIC CELLS IN DISEASE
• PART VI: DC-BASED THERAPIES
• Annotated References by Year
• Index