T cell activation and polarization by DC1 and DC2.

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells, capable of activating naive T helper (TH) cells [1-3]. Differentiation of activated TH cells into IFN-γ producing effector TH1 cells or IL-4, -5 and -10 producing effector TH2 cells depends respectively on cytokines, such as IL-12 or IL-4, possibly produced by a third cell type [3-7] IL-12 produced by activated macrophages was believed to be critical for TH1 differentiation [5-7]. Because IL-4 is a TH2 prototype cytokine, the original source of IL-4 required for TH2 differentiation has been controversial [4, 5]. During early cognate DC-T cell interaction, activated T cells rapidly express T cell activation antigen, CD40ligand [8-10]. The finding that CD40-ligand and microbial product rapidly induce DCs to produce a large amount of IL-12 suggests that dendritic cells may not need a third cell type to polarize activated T cells towards TH1 effectors [11-14]. The questions are: i) are there distinct types of DCs? ii) Do distinct types of DCs induce different types of immune responses, such as TH1 versus TH2 or immunity versus tolerance? iii) how do cytokine microenvironment or innate immunity determine the functions of DCs? iv) is there an IL-4 independent mechanism for the induction of TH2 differentiation? v) what are the ideal DCs for tumor therapy or for treatment of autoimmune diseases and graft versus host diseases (GVHD)?