{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:38:03Z","timestamp":1772930283290,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanisms of protective immunity to mycobacterial infection in the lung remain poorly defined. In this study, T-cell subset expansion and cytokine expression in bronchoalveolar spaces, lung parenchyma, and mediastinal lymph nodes of mice infected intratracheally with Mycobacterium bovis\u2013Calmette-Guerin bacillus (BCG) were analyzed in parallel with histopathology and bacterial burden. M. bovis\u2013BCG was cleared rapidly from bronchoalveolar spaces without evidence for persistence. In lung parenchyma bacteria grew during the first 4 wk followed by gradual clearance with less than 0.1% of the original inoculum persisting for more than 8 mo. Clearance of M. bovis\u2013BCG from bronchoalveolar lavage was associated with recruitment of both neutrophils and lymphocytes. Lung CD4+, CD8+, and \u03b3\u03b4 T-cell receptor\u2013positive T cells expanded maximally by Week 4, and declined by Week 8 to control values despite bacterial persistence. Both CD4+ and CD8+ lung T cells produced interferon (IFN)-\u03b3 in response to M. bovis\u2013BCG. Four distinct pathologic states of lung parenchymal infection were noted. Early focal sub-bronchial inflammation with transmigration of cells into airways was followed by diffuse peribronchitis, perivasculitis, and alveolitis with activated macrophages, lymphoblasts, and occasional giant cells. The latter stage corresponded to maximal M. bovis\u2013BCG growth. Resolving infection consisted of small lymphocytes and foamy macrophages, which coincided with decreasing M. bovis\u2013BCG colony-forming units, T-cell infiltration, and IFN-\u03b3 expression. A final quiescent phase consisted of residual lymphoid aggregates and perivasculitis associated with persistent spontaneous IFN-\u03b3 production. Bacterial dissemination to lymph node and spleen occurred by Week 4 and declined in parallel to lung. In contrast to lung, IFN-\u03b3 secretion was detected only late despite early expansion of CD4+ and CD8+ T cells. By reverse transcriptase\/polymerase chain reaction, IFN-\u03b3 and interleukin (IL)-12 p40 messenger RNA (mRNA) in lung paralleled IFN-\u03b3 protein production. Tumor necrosis factor-\u03b1, IL-4 and IL-10 mRNA expression was not increased during M. bovis\u2013BCG lung infection. Thus, protective immunity to M. bovis\u2013BCG in the lung evolved differently in air space, lung, and lymph node.<\/jats:p>","DOI":"10.1165\/ajrcmb.22.3.3776","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:39:08Z","timestamp":1365025148000},"page":"333-343","source":"Crossref","is-referenced-by-count":44,"title":["Pulmonary Immune Responses during Primary\n                    <i>Mycobacterium bovis<\/i>\n                    \u2013 Calmette-Guerin Bacillus Infection in C57Bl\/6 Mice"],"prefix":"10.1093","volume":"22","author":[{"given":"Scott A.","family":"Fulton","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and the Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and the Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond W.","family":"Redline","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and the Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Henry Boom","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and the Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026030700082429400_B1","first-page":"8","article-title":"Epidemiology of tuberculosis.","volume":"125","author":"Comstock","year":"1982","journal-title":"Am. 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