The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy

Optimal clearance of the various pathogen types encountered by the human bo dy requires the selective activation of particular cellular and/or humoral immune responses. The orchestration of the types of effector responses is d irected by Tn cells through the production of type 1 (Th 1 cell-associated) and type 2 (Th2 cell-associated) cytokines. The way in which the Th cell c ytokine profile is matched to the type of invading pathogen, and why these profiles sometimes derail and lead to disease, is not well understood. Here , we will discuss the concept that antigen-presenting cells (APC) provide T h cells not only with antigen and costimulatory signals, but also with a po larizing signal (signal 3). This signal can be mediated by many APC-derived factors, but IL-12 and PGE(2) seem to be of major importance. The Th2-bias ed responses in atopic allergy appeared to be associated with monocytes wit h a decreased IL-12/PGE(2) ratio and, consequently, with the down-regulatio n of type 1 cytokine production in Th cells. As for Th cells, APC can be fu nctionally polarized. In vitro experiments with monocyte-derived dendritic cells (DC) showed that the presence of IFN-gamma during activation of immat ure DC primes for mature DC with the ability of high IL-12 production and, consequently, a Th1-driving capacity (APC1 or DC1). In contrast, PGE2 prime s for a low IL-12 production ability and a Th2-driving capacity (APC or DC2 ). These findings suggest that pathogens provoke either Th1- or Tn2-cell de velopment by inducing the production of a certain pattern of inflammatory D C-polarizing mediators (e.g. IFN-gamma and PGE2) at the site of infection. The type of immune polarization will not only depend on the type of pathoge n. but also varies with the type of infected tissue, i.e. that different ti ssues produce different mediators in response to the same pathogen. In the case of atopic allergy, this concept implies that the Th2-cell bias may be related to low levels of cross-regulatory infections, to Th1 cell-inducing pathogens, or to an aberrant function of stromal cells in peripheral tissue s.