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-presentin g cells (APCs) has turned out to be the corresponding concept APC polarizat ion. 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 to wards either a Th1 or a Th2 phenotype, respectively. Among polarized APC, e ffector macrophages are classically activated by mediators such as IFN-gamm a, TNF-alpha or LPS (M phi1), while M phi2 are alternatively activated by I L-4, IL-10 or PGE(2). M phi2 exhibit a unique molecular repertoire includin g receptors of innate immunity with broad specificity for foreign antigen a nd anti-inflammatory cytokines such as IL-1 receptor antagonist and alterna tive macrophage activation-associated CC-chemokine (AMAC)-1. While DC1 are well characterized, contradictory results have been obtained for DC2 that m ay either represent immature myeloid DCs or lymphoid DCs. Altogether, APC2 have come to age; they mediate Th2 differentiation, tolerance induction, do wnregulation of inflammation and healing. Thus, APC2 represent a hitherto n eglected, but indispensable major pathway of APC activation and function. C opyright (C) 2001 S. KargerAG, Basel.