Jacques Banchereau, Beatrice Schuler-Thumer, A. Karolina Palucka, Gerold Schuler
Cell, Vol. 106, 271-274, August 10, 2001
Vaccines are composed of antigen(s) and adjuvant(s). Adjuvants play a critical role in determining the quantity and quality of the immune response to the antigen. Identification of appropriate adjuvants represents a universal problem in vaccine development.
For example, aluminum hydroxide (AlOH), currently the standard adjuvant for prophylactic vaccination to infectious diseases induces type 2 T cell (Th2) and antibody responses. However, Th2 immunity and antibody responses may be harmful.
Classic examples include Dengue and respiratory syncytial virus (RSV) vaccines that cause higher morbidity upon subsequent exposure to the virus in vaccinated (RSV) or naturally infected (Dengue) patients.
Furthermore, AlOH does not induce Th1 and cytotoxic T cell (CTL) responses that are necessary for effective antitumor immunity.
Other adjuvants such as QS-21, GM-CSF, and incomplete Freund's adjuvant have permitted, in some instances, specific CD8+ T cell responses when injected with tumor antigens; these responses were, however, detectable only after in vitro restimulation (Bendandi et al. 1999), (Rosenberg et al. 1998) and (Simon et al. 2001). Dendritic cells (DCs), the topic of this review, are “Nature's adjuvants” and, as such, represent an essential component of any vaccination strategy.
DCs were originally discovered as antigen presenting cells critical for the induction of primary T cell-dependent immune responses (Steinman, 1991).
Immature DCs in peripheral tissues, the Langerhans cell in the skin being the first example, can capture antigen(s) and can sense “danger” signals (pathogens, tissue damage, and local inflammation), which trigger their maturation. DCs process captured or intracellularly produced antigen(s) into peptides, migrate via afferent lymphatics to lymph nodes, and present MHC-peptide complexes to naive T cells (Banchereau et al. 2000) and (Steinman 1991). DCs also control the type of immune response, i.e., cytokines produced by helper or cytotoxic T cells: IFN-γ (type 1), IL-4 (type 2), or IL-10 (regulatory T cells).
Such control can be influenced by the subset of DC and the type and duration of the maturation signals they receive. Evidence is starting to accumulate for the role of DCs in the induction of immunological tolerance.
A provocative recent example is the observation that immature DCs are not simply ignored by the immune system, but can lead to tolerance by inducing IL-10 producing, regulatory T cells (Dhodapkar et al. 2001) and (Jonuleit et al. 2000). Therefore, the biology of DCs offer several targets for the control of cellular immunity.