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Immunology and vaccinology studies in mice are typically performed in naive specific pathogen-free animals responding to their very first respiratory challenge. We found that the first respiratory infection induces lifelong enlargement of the lung-draining mediastinal lymph nodes (medLNs). Furthermore, infection-experienced medLNs supported better naive T cell surveillance and effector responses to new unrelated infections that exhibited more biased accumulation and memory establishment within the lung. Moreover, we observed that weight loss induced by influenza infection was substantially reduced in mice that had recovered from a previous unrelated respiratory viral challenge. These data show that the lack of infectious history and corresponding medLN hypoplasia in specific pathogen-free mice alter their immune response to lung infections. Preclinical vaccination and immunology studies should consider the previous infectious experience of the model organism.<\/jats:p>","DOI":"10.4049\/jimmunol.2400010","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T13:05:47Z","timestamp":1713186347000},"page":"1621-1625","source":"Crossref","is-referenced-by-count":4,"title":["Cutting Edge: First Lung Infection Permanently Enlarges Lymph Nodes and Enhances New T Cell Responses"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-6413","authenticated-orcid":false,"given":"J Michael","family":"Stolley","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, 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