{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:39:45Z","timestamp":1776040785252,"version":"3.50.1"},"posted":{"date-parts":[[2023,12,21]]},"group-title":"Immunology","reference-count":157,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Immunological priming \u2013 either in the context of prior infection or vaccination \u2013 elicits protective responses against subsequent\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (\n                  <jats:italic>Mtb<\/jats:italic>\n                  ) infection. However, the changes that occur in the lung cellular milieu post-primary\n                  <jats:italic>Mtb<\/jats:italic>\n                  infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior\n                  <jats:italic>Mtb<\/jats:italic>\n                  infection elicits a long-lasting protective response against subsequent\n                  <jats:italic>Mtb<\/jats:italic>\n                  exposure and that the depletion of CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells prior to\n                  <jats:italic>Mtb<\/jats:italic>\n                  rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating\n                  <jats:italic>Mtb<\/jats:italic>\n                  disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, but also modulate innate immune cells to limit\n                  <jats:italic>Mtb<\/jats:italic>\n                  disease.\n                <\/jats:p>","DOI":"10.1101\/2023.12.20.572669","type":"posted-content","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T20:25:35Z","timestamp":1703190335000},"source":"Crossref","is-referenced-by-count":4,"title":["CD4\n                  <sup>+<\/sup>\n                  T cells are homeostatic regulators during\n                  <i>Mtb<\/i>\n                  reinfection"],"prefix":"10.64898","author":[{"given":"Joshua D.","family":"Bromley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharie Keanne C.","family":"Ganchua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"Nyquist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Maiello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Jacob","family":"Borish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Rodgers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Tomko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara","family":"Kracinovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douaa","family":"Mugahid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Son","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob 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