Figure 3. Model of T_H1 and T_H17 cell differentiation.

A. | Naive T cells differentiate in the presence of transforming growth factor-β (TGFβ), interleukin-1 (IL-1), IL-6 and IL-21 into an early T helper 17 (T_H17) cell stage that also produces IL-10 and IL-17. IL-4, IL-12, IL-27 and interferon-γ (IFNγ) inhibit T_H17 cell differentiation, and IL-21 acts in an autocrine manner at this stage. IL-23 promotes T_H17 cell differentiation, decreases IL-10 production and stabilizes the IL-17-producing phenotype. IL-23 may facilitate co-expression of IFNγ under some circumstances. IL-27 can suppress IL-17 and induce IL-10 production by T_H17 cells. B | Differentiation of T_H1 cells occurs in the presence of IL-12 and IL-18, with IFNγ acting in an autocrine manner. T_H1 cell differentiation is inhibited by IL-4, and IL-27 can enhance IFNγ production by differentiating T_H1 cells. Exposure to IL-12 and IL-27 induces differentiated T_H1 cells to produce IL-10 and IFNγ. Differentiated T_H17 and T_H1 cells express other pro-inflammatory cytokines (not depicted). Ca | Myelin-specific T cells with a low T_H17 to T_H1 cell ratio are primed in the periphery and infiltrate the meninges of both the brain and spinal cord. The T cells enter the spinal cord parenchyma and induce inflammation in an IFNγ-mediated signalling-dependent manner. The few T cells that enter the brain parenchyma, where IFNγ-mediated signalling inhibits inflammation, do not recruit inflammatory cells. Cb | Myelin-specific T cells primed in the periphery with a high T_H17 to T_H1 cell ratio infiltrate the meninges and parenchyma of both the brain and spinal cord. The higher T_H17 to T_H1 cell ratio in the brain is associated with a disproportionate increase in IL-17 production compared with the spinal cord, which may overcome the inhibitory IFNγ-mediated signalling in the brain parenchyma.