Development of th 1- or th 2-dominated immune responses: what about the polarizing signals?

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Type 1 helper T cells and type 2 helper T cells represent two extremely polarized forms of the effector specific immune response, based on a distinctive profile of cytokine production. Type 1- and type 2 helper T cell-dominated immune responses play a different role in both protection and immunopathology. The differentiation of effector phenotypes depends on a complex matrix of inter-connecting factors resulting from the evolutionary interplay between vertebrates and microorganisms. These include the physical form of the antigen, as well as the density and affinity of the peptide ligand, the cytokines produced by “natural” immunity cells at the time of antigen presentation, costimulatory signals provided by antigen-presenting cells, and hormones released into the microen-vironment. The elucidation of genetic and environmental factors that regulate type 1 or type 2 helper T cell development in response to different antigenic stimulation is the basis for new immunotherapeutic strategies in allergic and autoimmune disorders, as well as for the improvement of vaccines.