image: Upon IAV infection, lung CD8⁺ tissue-resident memory T (TRM) cells upregulate residency-associated gene signatures but exhibit increased apoptosis. A subset of these cells undergoes CCR5–CCL5 axis-dependent retrograde migration from the lung to the dLN, where they are maintained with reduced apoptotic activity and preserved TRM transcriptional identity. During secondary challenge, dLN TRM cells become reactivated, re-differentiate into TRM, and replenish the local TRM pool. This retrograde migration supports the dynamic maintenance of antiviral TRM populations in the respiratory tract.
Credit: ©Science China Press
A new study has uncovered how the body preserves long-term immune memory in the lungs after viral infection. Researchers from Tsinghua University and Changping Laboratory found that after influenza infection, a group of immune cells known as memory T cells do not simply remain in the lungs. Instead, they actively migrate to nearby lymph nodes, where they form a stable reservoir ready to respond to future infections.
These cells, called tissue-resident memory T cells (TRM), are essential for rapid local immune protection. Using advanced single-cell tracking techniques in a mouse model, the team observed that TRM cells in the lungs share the same identity and gene expression as those found in lung-draining lymph nodes. This suggests that lung TRM cells move back into the lymph nodes in a process called retrograde migration.
The researchers identified the chemokine receptor CCR5 as the key molecule guiding this movement. Blocking CCR5 using the drug Maraviroc significantly reduced the number of memory T cells in the lymph nodes without affecting those in the lung. The study shows that these lymph node-based TRM cells can later migrate back into the lung during reinfection, replenishing the local defense force.
“This study reveals a dynamic maintenance loop between the lung and lymph node,” said corresponding author Hai Qi. “It provides a new perspective on how the immune system preserves frontline defenses in the respiratory tract.”
These findings offer new insight into respiratory immunity and may help guide the design of next-generation vaccines aimed at enhancing long-term protection in the lungs.
About the institutions:
Tsinghua University is one of China’s leading research universities with global impact in science and technology. Changping Laboratory focuses on biomedical innovation and translational medicine to address critical healthcare challenges.
Journal
Science China Life Sciences
Method of Research
Experimental study