The Th1-Th2 paradigm in 1998: law of nature or rule with exceptions.

is the production of IL-12 by macrophages and dendritic cells responding to antigens or direct infection immune response; transplantation [3]. Polarized Th1 cells produce IL-2, IFN-c, and lymphotoxin. These cytokines promote the development of cytotoxic T cells, which support delayed-type hypersensitivity reaction (DTH) and facilitate anti-body-dependent cellular cytotoxicity (ADCC) serving Twelve years ago Mosmann and Coffman described as effector mechanisms against intracellular pathogens individual CD4+ T-cell clones in mice that produced and allotransplants (Figure 1). distinct profiles of cytokines [1]. A link between the Stimulation of naive CD4+ T cells by T cell receptor different patterns of cytokine production of the two T ligation in presence of IL-4 leads to Th2 differentiation helper subsets, termed Th1 and Th2, and their distinct-[4]. Besides naive T cells themselves, mast cells and a ive functions has been observed. Th1 cells are mainly rare population of NK1.1.+ CD4+ T cells are believed involved in cell-mediated immunity, whereas Th2 cells to be the initial source of IL-4. Polarized Th2 cells are commonly found in association with humoral produce IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 immune responses. In certain situations, Th2 cytokines and have important effects on immunoglobulin isotype are antagonistic to Th1 cell development and function expression. In mice, Th2 responses stimulate IgE and and Th1 cytokines inhibit Th2 responses. This Th1-IgG1 production by B cells and activate eosinophils, Th2 paradigm has stimulated intensive efforts to under-thereby promoting anti-helminthic and allergic immune stand how CD4+ T cell activation program regulates responses (Figure 1). the immune response towards Th1-or Th2-type. A large body of evidence suggests that Th1-Moreover, targeted manipulations of the cytokine net-dominated immune response inhibits the Th2-work have been suggested for the development of new dominated arm and vice versa [5]. For example, the therapeutic strategies to inhibit allograft rejection, to Th1 cytokine IFN-c blocks antigen-induced prolif-induce tolerance, to prevent and treat autoimmune eration of Th2 cells and inhibits IL-4-and IL-5-diseases, and also to enhance vaccination efficacy. dependent B lymphocyte differentiation. In contrast, However, in many situations, mechanisms underlying IL-4 inhibits Th1 cell development by antagonizing the immune response obviously exist that seem to many of the activities mediated by IFN-c. ignore the Th1-Th2 paradigm. Strong evidence exists that both Th1 and Th2 cells It has been suggested that tolerance to an allograft derive from a common Th0 precursor. Genetic factors may be achieved by immune deviation of CD4+ T cells and …