Cytokines are a group of regulatory proteins critically involved in many physiological processes such as immune recognition, cell differentiation and cell proliferation. They have been identified in many vertebrate species and are produced by a variety of different cell types. Cytokines are usually produced transiently and locally, and act paracrine or autocrine. They interact with high affinity cell surface receptors specific for each cytokine or cytokine group and are active at very low concentrations, usually in the picogram range. It is well known that the type of antigen-specific immune response largely depends on the selection or preferential activation of defined CD4+ T helper cell subsets (i.e. Th1 and Th2). Activation of these subsets is characterized by the secretion of different patterns of cytokines.
Figure T helper 1 pathway
Th1, but not Th2 cells, mainly secrete IL-2 and IFN-γ, while Th2, but not Th1 cells, produce IL-4, IL-5, IL-6, IL-10 and IL-13. Other cytokines, such as TNF-α and GM-CSF are produced by both Th subsets. In addition, the production of IL-12 and IL-10, produced by antigen presenting cells (APC) such as macrophages and dendritic cells, critically contributes to the preferential expansion of Th1- or Th2-type of cells. For instance, early production of IL-12 is considered essential for the development of Th1 cells. On the other hand, the absence or low concentrations of IL-12 and IFN-γ in the early phase of an immune response and concomitant production of IL-4 by cells of the mastcell/basophil lineage or T cells themselves is known to favor the development of Th2 cells. In addition to their regulatory effects on Th subset differentiation, the cytokines released by the two types of Th cells also produce different effector functions. For example, IL-4 and IFN-γ have differential or antagonistic activities on immunoglobulin isotype selection or MHC class II expression. Therefore, the characteristics of an immune response are best studied by determining the amounts of cytokines produced by the responding T cells and APC.