Immunotherapy for Infectious Diseases

From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
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Dendritic Cells
Their Role in the Immune Response to Infectious Organisms and
Their Potential Use in Therapeutic Vaccination
Smriti K. Kundu-Raychaudhuri and Edgar G. Engleman
INTRODUCTION
The ability of the immune system to recognize and eliminate infectious agents has
been well established. As detailed in the other chapters of this monograph, both humoral
and cellular immune responses contribute to the elimination of infection. Over the past
decade, our own research has focused on a critical component of the cell-mediated
immune system, bone marrow-derived dendritic cells (DCs). At least two distinct populations
of such DC have been described, including the classical and more numerous
myeloid DC and the recently described plasmacytoid or Interferon-� secreting DC.
Most studies of DC completed in the past two decades have not distinguished between
these two populations, but because myeloid DC account for approx 90% of DC obtained
from sources such as blood and lymphoid organs, the functions attributed to DC mainly
reflect myeloid DC activity. Unless otherwise indicated, this report summarizes our current
understanding of the functions of myeloid DC.
DCs are extremely potent antigen-presenting cells (APCs) that initiate immune
responses to pathogens by taking up, processing, and presenting antigens to T-cells.
Present in all tissues except the brain, DCs serve as sentinels for the immune system
and (particularly in the skin, mucosal sites, and lung) are among the earliest cell populations
to come into contact with invading organisms. When activated by antigen and
“danger signals,” DCs in peripheral tissues carry antigens via the lymphatic system into
the T-cell regions of draining lymph nodes, where they stimulate primary and memory
T-cell responses (1). DCs are also central to the development of antibody responses
because of the requisite role of activated helper T-cells in the differentiation of B-cells
(2,3). Through their activation of helper and cytolytic T-cells and the subsequent interaction
of T-helper cells with B-cells, DCs dictate both the nature and potency of the
immune response.
DCs are in effect nature’s adjuvant. They are not only capable of inducing antigenspecific
helper and cytotoxic T-cell responses, they also produce a cytokine, interleukin-12
(IL-12), and chemokines such as RANTES and fractalkine. IL-12 skews the T-cell response