Fig.4. A diverse array of T cell effector lineages contributes to granulomatous vasculitis.

The population of T cells attracted to and retained in the inflamed vessel wall is assembled from many different T cell lineages. A series of different lineage-defining effector cytokines are produced in the lesions (A). T cells producing IFN-gamma, IL-21 or GM-CSF are mostly encountered in the adventitial layer. Effector T cell populations interact with multiple target cell populations (B). T cells attract, activate and sustain tissue-resident and tissue-infiltrating macrophage populations. Effector T cells interact with and receive stimulatory signals from endothelial cells. Effector T cell populations regulate pathways that involve stromal cell populations and lead to vascular remodeling, such as microvascular angiogenesis and intimal hyperplasia. Arrows indicate interactions that have been demonstrated or are suspected. The heterogeneity of effector T cells speaks against a single antigen driving GCA. One factor allowing the expansion of multiple effector lineages in the vascular lesions is the deficiency of the inhibitory PD-1/PD-L1 immune checkpoint. (Illustration credit: Sceyence Studios)