Role of Th1 and Th2 in autoimmunity

With regard to the ability of T helper (Th) CD4 + cells to regulate, instruct, and enhance specific functions of their cell targets based on environmental threats, these cells are orchestra leaders of the adaptive immune response. Within this well-studied lymphocyte class, the presence of various subsets, with a major role in health and disease has been recognized. Among these, Th1 and Th2 were the first to be described. More recently, Th17, T regulatory, T follicular helper, and other subsets were also discovered. Th1 T cell's main cytokines are IFN-γ, IL-2, and TNF-α, which can induce classical activation of macrophages and their phagocytic activity. Besides, they stimulate further Th1 polarization and IgG2 and IgG3 isotype switch. The consequent Th1 immune response provides, under physiological conditions, protection from viruses, intracellular bacteria, and protozoa. However, it can be involved in several autoimmune disorders, such as type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, and Crohn's disease. Recently, the pathogenic role of Th1 cells has been challenged by new findings of Th17 functions and plasticity, in particular the existence of ex-Th17 cells which acquire a Th1-like phenotype. On the other side, Th2 T cells are characterized by the production of a different spectrum of soluble mediators, mostly IL-4, IL-5, and IL-13. IL-4 and IL-13 lead to alternative macrophage activation, which is involved in tissue repair and fibrosis. IL-5 leads to recruitment, survival, and activation of eosinophils. Overall, the Th2 response provides defense against helminths, favors the IgE isotype switch, and stimulates physical mechanisms of protection in the gut as well as airways. However, a dysregulated Th2 response is associated with a wide range of diseases, such as atopic dermatitis, asthma, and anaphylaxis.