ABSTRACT

I. ROLE OF DENDRITIC CELLS Dendritic cells (DC) are a sparse population of bone marrow-derived antigen-presenting cells, irregular in shape and widely distributed in both lymphoid and nonlymphoid tissues [1,2]. Those having migrated to nonlymphoid tissues such as the epidermal layer of the skin, the respiratory and gastrointestinal systems, and interstitial regions of solid organs are considered immature. Fully mature DC are located in lymphoid organs. After antigen internalization and inflammation, DC leave the tissues interfacing with the external environment and enter the lymphatic vessels to reach the lymphoid organs and undergo maturation [1-3]. While still immature, the primary function of DC is to phagocytize and process antigens, then to present the antigenic peptides and activate specific T cells [1,2]. Activation of naive T cells requires two signals. The first signal is delivered when the TCR engages the MHC/antigen complex, and the second, costimulatory signal is delivered by costimulatory molecules on DC [4]. Failure to deliver a costimulatory signal with antigen presentation induces a state of T-cell anergy [5]. At least two potent costimulatory signal pathways are essential for normal development and maintenance of immunity. In one system CD40 on DC interact with CD40 ligand (CD154) proteins expressed on activated T cells. In the B7/CD28 pathway, DC surface B7.1 (CD80) and B7.2 (CD86) molecules deliver a costimulatory signal by interacting with the CD28 cell surface protein expressed on resting T cells [4,6]. Activation of naive T-helper (Th) cells results in their polarization toward the Th1 and/or Th2 type, which orchestrates the immune effector mechanism that is more appropriate for the invading pathogen. Th1 cells promote cellular immunity,

protecting against intracellular infection and cancer, but carry the risk of organ-specific autoimmunity. Th2 cells promote humoral immunity, highly effective against extracellular pathogens, and are involved in tolerance mechanisms and allergic diseases. The initiation and type of adaptive immune responses is controlled by innate immune recognition, which is mediated by DC that produce interleukin-12 (IL-12), a prerequisite for both the activation of innate immunity and the development of Th1 responses [7,8].