Airway-resident memory CD4 T cell activation accelerates antigen presentation and T cell priming in draining lymph nodes
Caroline M. Finn, Kunal Dhume, Eugene Baffoe, Lauren A. Kimball, Tara M. Strutt, K. Kai McKinstry
Caroline M. Finn, Kunal Dhume, Eugene Baffoe, Lauren A. Kimball, Tara M. Strutt, K. Kai McKinstry
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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

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 4

IAV-primed CD4 Trm rapidly respond to antigen in adoptive host mice after i.n. transfer.

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IAV-primed CD4 Trm rapidly respond to antigen in adoptive host mice afte...
(A) The number of OT-II Trm in mice receiving naive OT-II cells i.v. on stated days after IAV priming (black) and the number of OT-II Trm in unprimed host mice 1 day after i.n. transfer of OT-II memory cells isolated from lungs of IAV-primed mice (open); n = 3 mice/group/time point. (B and C) Representative labeling of lung OT-II memory cells in primed mice at 45 dpi (left) and donor OT-II Trm in host mice 1 day after transfer (right) by noncompeting anti-CD4 Ab clones given i.n. and i.v. before lung harvest (B), and number of nonlavagable and lavagable donor Trm from unprimed host mice 1 day after transfer (C); n = 8/group; pooled from 2 experiments. (D) CD69 (left) and CD25 (right) expression by donor Trm subsets 6 hours after i.n. administration of FITC-OVA or PBS alone; n = 3–4/group; 1 of 3 experiments. (E) Levels of stated analytes in lung homogenates from mice receiving Trm or not 20 hours after FITC-OVA administration; dotted lines are average levels from mice receiving PBS alone; n = 4/group; 1 of 3 experiments. (F) Numbers of stated cell types in lungs of mice harboring Trm or not 20 hours after FITC-OVA administration; n = 4/group; 1 of 2 experiments. (G and H) Numbers of FITC+ DC in lungs (n =4/group; 1 of 2 experiments) (G) and dLN (n =6/group; pooled from 2 experiments) (H) 20 hours after FITC-OVA administration to unprimed mice harboring OT-II Trm or not. (I) CD40, CD80, and CD86 expression by FITC+ DC in the dLN; n = 3/group; 1 of 3 experiments. Student’s t test was used for pairwise comparison in all panels except D, where 1-way ANOVA with Tukey’s multiple-comparison test was used. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.