A lymphoid tissue chemokine checkpoint prevents loss of CD8+ T cell functionality
Altenburger, L. M.; Claudino Carvoeiro, D.; Dehio, P.; Zhou, J.; Laura, C.; Katoch, M.; Krueger, C.; Barreto de Albuquerque, J.; Pfenninger, P.; Martinez Magdaleno, J.; Abe, J.; Mehling, M.; Dengjel, J.; Iannacone, M.; Hashemi Gheinani, A.; Stein, J. V.
Show abstract
The generation of effector CD8+ T cells (TEFF) requires activation of naive CD8+ T cells (TN) by dendritic cells (DCs) within lymphoid tissue. To date, it remains elusive how the duration of TN-DC interactions and integration of activation signals are controlled in vivo. Here, we report that lymphoid stroma-secreted ligands for CCR7 constrained interaction duration by gradually inducing CD8+ T cell release from DCs. At late time points of interactions, CCR7 ligands repositioned the F-actin-promoting factor DOCK2 away from the DC interface to enable CD8+ T cell detachment, proliferation onset and acquisition of cytotoxicity. Lack of CCR7 signaling, as during ex vivo activation or in chronically inflamed lymphoid tissue, caused sustained T cell-DC interactions, and generated dysfunctional TEFF with high expression of inhibitory receptors, impaired antimicrobial activity, and poor recall responses. In sum, our findings uncover that lymphoid stromal chemokines act as built-in "disruptors" of T cell-DC interactions for long-term preservation of TEFF functionality.
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