It seemed that Th1 and Th2 cells represented mutually exclusive binary epigenetic states because IL-12, IFN-γ, and the expression of T-bet inhibited Th2 differentiation, whereas IL-4 and Gata3 expression antagonized Th1 polarization. 12-14 Th2 cells, induced by IL-4 via Stat6 signaling that up-regulates the transcription factor GATA3, 15, 16 were linked to humoral responses to extracellular organisms or parasites and development of atopy and allergic reactions, 17-20 producing cytokines that include IL-4, IL-5, and IL-13.
#Kimball organ schematics 732 Activator#
10, 11 Th1 cells are promoted by interleukin (IL)-12 (via signal transducer and activator of transcription 4) signaling and interferon (IFN)-γ (via Stat1), which induce the expression of master transcription factor T-box 21 ( tbx21, T-bet) and secretion of the hallmark cytokine IFN-γ. 9 Th1 cells were considered essential for antiviral immunity and for providing help to CD8 + cytotoxic T cells and were viewed as the main perpetrators of autoimmunity. In their early descriptions of the Th1/Th2 paradigm, Mossman, Coffman and colleagues 6 -8 attempted to explain responses observed in many experimental models of infection, autoimmunity, and allergy. New findings indicate that subset polarization of CD4 + T cells not only induces characteristic patterns of surface markers and cytokine production but also has a maturational aspect that affects a cell’s ability to survive, respond to secondary stimulation, and form long-term immune memory.
Moreover, plasticity of this subset is associated with higher in vivo survival and self-renewal capacity and less senescence than Th1 polarized cells, which have less plasticity and more phenotypic stability. This late plasticity may contribute to the protection against microbes, plays a role in the development of autoimmunity, and is necessary for antitumor activity of Th17 cells in adoptive cell transfer therapy models. Th17 cells display a great degree of context-dependent plasticity, as they are capable of acquiring functional characteristics of Th1 cells. Th17 cells express the master transcriptional regulator retinoic acid–related orphan receptor γ thymus and produce canonical interleukin (IL)-17A and IL-17F cytokines. These polarization states include Th1, Th2, Th17, and Foxp3 + T regulatory cells, as well as the more recently described T follicular helper, Th9, and Th22 cells. CD4 + T helper (Th) cells exist in a variety of epigenetic states that determine their function, phenotype, and capacity for persistence.