Figure 2. Interferon γ-dependent regulation of pro-inflammatory T cell responses in the heart.

Although T_H1 cells, as well as T_H17 cells, contribute to acute and chronic inflammatory damage to the myocardium in infectious and autoimmune myocarditis, IFNγ production by T_H1 cells exerts several feedback regulatory effects that dampen T cell activation and effector functions. IFNγ induces PD-L1 on myocardial endothelial cells (and possibly myocytes) which inhibits effector T cell activation by binding to PD-1 on the T cells. IFNγ together with TLR ligands promote the differentiation of TNF and iNOS producing DCs (Tip DCs) which, through the action of NO, inhibit effector T cell proliferation. IFNγ also blocks the differentiation of T_H17 cells. The absence of IFNγ or its receptor exacerbates disease in experimental infectious and autoimmune myocarditis.