Lymphoid Chemokine Checkpoint: CD8+ T Cell Guard
Activation of naive CD8+ T cells (TN) by pMHC-presenting dendritic cells (DCs) in lymphoid tissue is key to effector CD8+ T cell (TEFF) generation. How the duration of TN-DC interactions, and thereby integration of activation signals, is controlled in vivo remains elusive. Here, we report that lymphoid stroma-secreted ligands for CCR7, a TN-expressed chemokine receptor, act as rheostat of interaction duration by gradually inducing CD8+ T cell release from DCs. At late time points of interactions, CCR7 ligands promoted redistribution of the F-actin-promoting factor DOCK2 away from the immunological synapse to enable CD8+ T cell detachment, onset of proliferation and acquisition of cytotoxic capacity. Defects in the CCR7 rheostat caused sustained TN-DC interactions, yielding TEFF with high inhibitory receptor expression and impaired antimicrobial activity. In sum, our results uncover an evolutionarily conserved lymphoid tissue chemokine checkpoint that restricts TN-DC interactions to safeguard TEFF differentiation and to prevent imprinting of dysfunctional traits.