Fig. 2.
T cell activation and migration to non-lymphoid tissues. (a) Antigens are presented to naïve T cells either by migratory DCs, which collect antigens in the peripheral tissues, mature, and migrate into the lymph nodes, or by lymph node-resident DCs that take up antigens transported in solution with the lymph. (b) Activated T cells exit from lymph nodes reaching first venous and then arterial blood and home into inflamed tissue chasing a gradient of inflammatory chemokines thanks to the expression of the corresponding chemokine receptors. Once in the proximity of the inflamed tissue, T cells adhere to the vascular endothelium first through weak interactions with endothelial selectins, such as E- and P-selectin, and then arresting their rolling by binding with integrins to endothelial adhesion molecules. Stable adhesion is followed by extravasation guided by the chemokine gradient and the upregulation of CD69 expression. (c) Upon activation naïve T cells start to proliferate and differentiate into effector cells, which migrate to peripheral tissues where they perform their effector function. Once the antigen has been eliminated, the large majority of effector cells die by apoptosis, while a small fraction of antigen-specific T cells persists as TCM, TEM, or TRM cells, which are characterized by a tropism toward different anatomic sites, to provide systemic and local long-term protection