Lymphoid tissue chemokines limit priming duration to preserve CD8⁺ T cell functionality

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Effector CD8+ T cell (T_EFF) generation depends on naïve T cell (T_N) activation by dendritic cells (DCs) in lymphoid organs.
• The mechanisms controlling T_N-DC interaction duration and signal integration are not fully understood.

Purpose of the Study:

• To investigate how T_N-DC interaction duration is regulated.
• To elucidate the role of CCR7 ligands in controlling T cell priming and effector function.

Main Methods:

• Investigated T_N-DC interactions in lymphoid tissue.
• Analyzed the role of CCR7 ligands and DOCK2 in T cell detachment and activation.
• Assessed T_EFF function following disruption of CCR7 signaling.

Main Results:

• Lymphoid stroma-secreted CCR7 ligands limit T_N-DC interaction duration by promoting T cell release.
• CCR7 ligands induce DOCK2 relocalization from the DC interface, enabling T cell detachment, proliferation, and cytotoxicity.
• Disrupted CCR7 signaling leads to prolonged T_N-DC contact and generates dysfunctional T_EFF with impaired antimicrobial and recall responses.

Conclusions:

• Stromal chemokines are critical regulators of T cell priming by DCs.
• CCR7 signaling ensures optimal CD8+ T cell effector function during acute and memory phases.