Dendritic cells: immunological sentinels with a central role in health and disease

Abstract

Immunological effector cells must be sensitive to the antigens or environmental signals that indicate that a pathogen is present. To this end, a group of cells known as the professional antigen-presenting cells have the ability to educate T, B and NK cells as to the fingerprints of specific infections. The most adept of these cells are a closely related family termed dendritic cells (DC). A subset of these act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material combined with an ability to detect a wide variety of 'danger' signals. These 'danger' or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. In the present review, a number of recent advances in the understanding of DC biology are discussed. These advances offer insights into the pathogenesis of a wide variety of diseases and point towards future strategies for immunotherapy.

Figure 1

Dendritic cell life history can be subdivided into a number of phases, all with discrete cellular functionality. Transition between phases is mediated by diverse signals and is accompanied by changes in expression patterns of many surface markers and secreted factors. MDC, myeloid dendritic cell; SCF, stem cell factor; GM‐CSF, granulocyte–macrophage colony stimulating factor; TGF, transforming growth factor; HSP, heat shock protein.

Figure 2

Interaction of dendritic cells with T lymphocytes. Antigen is presented as peptide MHC class‐I/II complexes (signal 1). T lymphocytes are activated by the presence of costimulatory molecules, which communicate that the presented antigen is associated with a ‘threat’ (signal 2). Absence of these secondary signals induces tolerance towards the presented peptide. LFA, leucocyte functional antigen; ICAM, intercellular adhesion molecule; VLA, very late antigen.

Figure 3

Dendritic cell immunotherapy of cancer. A state of immunological tolerance usually exists between the tumour and the host. Infusions of activated, tumour antigen‐loaded dendritic cells (DC) stimulate the proliferation of antigen‐specific anti‐tumour CTL.