Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing

The Th1/Th2 paradigm has stimulated extensive research into the mechanisms underlying T-cell polarization; alternative activation of antigen-presenting cells (APCs) has turned out to be the corresponding concept APC polarization. Macrophages (M phi) as well as dendritic cells (DCs) can undergo Th1- or Th2-like polarization; APC1 and APC2 thus acquire the capacity to drive the development of naive T cells and the reactivation of resting T cells towards either a Th1 or a Th2 phenotype, respectively. Among polarized APC, effector macrophages are classically activated by mediators such as IFN-gamma, TNF-alpha or LPS (M phi 1), while M phi 2 are alternatively activated by IL-4, IL-10 or PGE(2). M phi 2 exhibit a unique molecular repertoire including receptors of innate immunity with broad specificity for foreign antigen and anti-inflammatory cytokines such as IL-1 receptor antagonist and alternative macrophage activation-associated CC-chemokine (AMAC)-1. While DC1 are well characterized, contradictory results have been obtained for DC2 that may either represent immature myeloid DCs or lymphoid DCs. Altogether, APC2 have come to age; they mediate Th2 differentiation, tolerance induction, downregulation of inflammation and healing. Thus, APC2 represent a hitherto neglected, but indispensable major pathway of APC activation and function.