Atopic Allergy: A Failure of Antigen-Presenting Cells to Properly Polarize Helper T Cells?

The immunological hallmark of adult atopic allergy is an aberrant production of helper T cell type 2 (Th2) cytokines interleukin 4 (IL-4), IL-5, IL-9, and IL-13 by Th cells reacting to common environmental antigens (1, 2). Mouse model experiments suggest strongly that airway hyperreactivity depends on IL-13 (3) and airway inflammation depends on IL-5 (4). In fact, the bias to type 2 cytokine production in atopic allergy is generalized (5), and an important issue is why these cells have developed in atopic allergic individuals. Th2 cells are effector Th cells that develop from naive Th cells after activation in the presence of certain polarizing signals. A first activation signal (signal 1) is the recognition by the T cell receptor of antigenderived peptides presented in association with MHC molecules expressed by antigen-presenting cells (APCs). An obligatory second signal (signal 2) for these primary T cells is costimulation through the ligation of CD28 by B7.1 or B7.2, expressed by APCs as well. Primary Th cells do produce low levels of Th1 (e.g., interferon g [IFNg ], tumor necrosis factor b [TNFb ]) and Th2 cytokines, but these cytokines will be produced after one or more cell cycles and the concomitant maturation into effector Th cells. Polarization into either Th1 or Th2 cytokine production can be induced by various soluble or membrane-bound molecules, constituting a set of polarizing activities, acting as a third signal (signal 3) during the initial activation of naive Th cells. The process of polarization can occur early, since already within a few days after the initiation of the immune response lymph nodes contain polarized T cells (6). Here we discuss the perspective that the aberrant Th2 cell development in atopic allergy follows from a failure in the Th cell polarization by APCs.