Follicular Helper CD4⁺ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

Figure 1

Effector subsets of CD4⁺ T cells: ontogenic and major cytokines, and roles in diseases. Naive CD4⁺ T cells differentiate into diverse effector subsets dependent on stimulatory cytokines in the microenvironment upon activation by pathogens. These stimulatory cytokines induce transcription factors expression of these subsets. IL-12 induces T-bet in the case of Th1 cells, IL-4 induces GATA3 in the case of Th2 cells, TGF-β, IL-6, and IL-23 induce RORγt and RORα in the case of Th17 cells, TGF-β induces Foxp3 in the case of Treg cells, and IL-6 and IL-21 induce Bcl-6 in the case of TFH cells. Subsequently, different effector subsets produce distinct cytokines and acquire specialized effector function. Th1 cells produce IFN-γ associated with antiviral and antibacterial immunity and cell-mediated immunity, Th2 cells produce IL-4 associated with immunity to extracellular parasites, Th17 cells produce IL-17 associated with inflammation, fungal immunity, and protection at mucocutaneous sites, Treg cells produce TGF-β and IL-10 associated with regulation, tolerance, and immune suppression, and TFH cells produce IL-21 associated with providing help for B cell differentiation and antibody production. Bcl-6, B cell lymphoma 6; Foxp3, forkhead box p3; GATA-3, GATA-binding protein 3; IFN-γ, interferon-γ; IL-4, interleukin 4; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; IL-21, interleukin 21; IL-23, interleukin 23; RORγt, retinoid-related orphan receptor γt; RORα, retinoid-related orphan receptor α; T-bet, T-box transcription factor; TGF-β, transforming growth factor-β; TNF, tumour necrosis factor; Treg, T regulator.