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Airway-resident memory CD4 T cell activation accelerates antigen presentation and T cell priming in draining lymph nodes
Caroline M. Finn, … , Tara M. Strutt, K. Kai McKinstry
Caroline M. Finn, … , Tara M. Strutt, K. Kai McKinstry
Published December 17, 2024
Citation Information: JCI Insight. 2025;10(3):e182615. https://doi.org/10.1172/jci.insight.182615.
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Research Article Immunology Inflammation

Airway-resident memory CD4 T cell activation accelerates antigen presentation and T cell priming in draining lymph nodes

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Abstract

Specialized memory CD4 T cells that reside long-term within tissues are critical components of immunity at portals of pathogen entry. In the lung, such tissue-resident memory (Trm) cells are activated rapidly after infection and promote local inflammation to control pathogen levels before circulating T cells can respond. However, optimal clearance of Influenza A virus can require Trm and responses by other virus-specific T cells that reach the lung only several days after their activation in secondary lymphoid organs. Whether local CD4 Trm sentinel activity can affect the efficiency of T cell activation in secondary lymphoid organs is not clear. Here, we found that recognition of antigen by influenza-primed Trm in the airways promoted more rapid migration of highly activated antigen-bearing DC to the draining lymph nodes. This in turn accelerated the priming of naive T cells recognizing the same antigen, resulting in newly activated effector T cells reaching the lungs earlier than in mice not harboring Trm. Our findings, thus, reveal a circuit linking local and regional immunity whereby antigen recognition by Trm improves effector T cell recruitment to the site of infection though enhancing the efficiency of antigen presentation in the draining lymph node.

Authors

Caroline M. Finn, Kunal Dhume, Eugene Baffoe, Lauren A. Kimball, Tara M. Strutt, K. Kai McKinstry

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Figure 1

IAV-primed lung CD4 Trm respond rapidly to i.n. administered antigen.

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IAV-primed lung CD4 Trm respond rapidly to i.n. administered antigen.
(A...
(A) B6 mice received 1 × 106 naive CD90.1/CD90.2 OT-II cells i.v. followed by priming with PR8-OVAII. After 45 days, the primed mice were challenged with i.n. administered antigen to recall OT-II Trm in the lung. (B) Primed mice were treated at 45 dpi with fluorescent anti-CD4 Ab i.v. prior to lung harvest, with representative staining shown to identify donor OT-II cells (left), donor Trm shielding from labeling by i.v. administered CD4 Ab (center), and expression of CD69 by the i.v.shielded versus i.v.labeled OT-II cells (right). (C) Number of donor Trm (i.v.shielded) cells in interstitial and airway niches based on BAL harvest; n = 7/group; pooled from 2 experiments. (D) IAV-primed mice were given 50 μg of OVA or BSA, or PBS alone via i.n. administration. Representative CD69 (left) and CD25 (right) staining of total lung OT-II Trm 6 hours later. (E) The percentage of CD69hi (left) and CD25hi (right) donor Trm in airway (circles) and interstitial (triangle) niches from separate mice given OVA or PBS: n = 4–5 per group; results from 1 of 3 experiments. Student’s t test was used for pairwise comparison for C, and 1-way ANOVA with Tukey’s multiple-comparison test was used in E. *P < 0.05, **P < 0.01, ****P < 0.0001.

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