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 2

Lung CD4 Trm activation enhances the number and activation status of antigen-bearing DC in the dLN.

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Lung CD4 Trm activation enhances the number and activation status of ant...
(A) Representative staining of FITC+MHC-II+ cells in stated organs 20 hours after FITC-OVA administration to IAV-primed mice harboring OT-II Trm. (B and C) Representative CCR7 expression by FITC+ and FITC– DC (B) and CD11b and CD103 expression by FITC+ DC to define DC1 and DC2 subsets (C). (D) frequency (left) and number (right) of FITC+ DC from stated mice 20 hours after antigen administration; n = 5/group; 1 of 2 experiments. (E) Frequency of DC2 within FITC+ DC of primed and unprimed mice receiving FITC-OVA; n = 7; results pooled from 2 experiments. (F) Representative staining of donor and host CD4 T cells in lungs of primed mice receiving FITC-OVA and isotype or CD4-depleting Ab treatment (left) and the number of FITC+ DC in the dLN (right); n = 4/group; 1 of 2 experiments. (G) CD69 expression by naive OT-II cells 48 hours after culture with stated subsets of sort-purified DC from IAV-primed mice 20 hours after FITC-OVA administration, with the percentage of CD69+ cells averaged from triplicate wells; 1 of 3 experiments. (H) Representative staining and MFI of CD40, CD80, and CD86 expression by FITC+ DC in dLN of primed mice after FITC-OVA or FITC-BSA administration, with shaded histograms and dotted lines in graphs for expression in mice receiving PBS; n = 4 per group; results from 1 of 3 experiments. (I) Numbers of FITC+ DC in dLN 20 hours after FITC-OVA administration to IAV-primed mice treated with stated Abs; n = 7/group; pooled results from 2 of 3 experiments. Student’s t test was used for pairwise comparison for all panels except I, where 1-way ANOVA with Dunnet’s multiple comparison test was used. *P < 0.05, **P < 0.01, ***P < 0.001.