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In this study, we infected mice with a genetically modified pneumonia virus of mice (PVM) that allowed visualization of virus-specific CTL and infected cells<jats:italic>in situ<\/jats:italic>. The first virus-specific T cells entered the lung via blood vessels in the scattered foci of PVM-infected cells, which densely clustered around the bronchi at day 7 after infection. At this time, overall pulmonary virus load was maximal, but the mice showed no overt signs of disease. On days 8 to 9, T cells gained access to the infected bronchial epithelium and to the lung interstitium, which was associated with a reduction in the number of virus-infected cells within the initial clusters but could not prevent further virus spread throughout the lung tissue. Interestingly, recruitment of virus-specific CTL throughout the parenchyma was still ongoing on day 10, when the virus infection was already largely controlled. This also represented the peak of clinical disease. Thus, disease was associated with an exuberant T cell infiltration late in the course of the infection, which may be required to completely eliminate virus at residual foci of infection. PVM-induced immunopathology may thus result from the need to generate widespread T cell infiltrates to complete the elimination of virus-infected cells in a large organ like the lung. This experimental model provides the first insights into the spatiotemporal evolution of pulmonary antiviral T cell immunity<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/jvi.00255-13","type":"journal-article","created":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T13:10:37Z","timestamp":1376572237000},"page":"11267-11275","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>In Situ<\/i>Evolution of Virus-Specific Cytotoxic T Cell Responses in the Lung"],"prefix":"10.1128","volume":"87","author":[{"given":"Stefanie","family":"Frey","sequence":"first","affiliation":[{"name":"Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanspeter","family":"Pircher","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Follo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Collins","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Krempl","sequence":"additional","affiliation":[{"name":"Institute of Virology and Immunobiology, Julius Maximilian University, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[{"name":"Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/421779"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(80)80799-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198607103150201"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb01010.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00375-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115362"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00699-08"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/152.4_Pt_2.S59"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.721"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02041-08"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00364-07"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.23.13362-13365.2004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.2.390-412.2004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2008.03.013"},{"key":"e_1_3_2_16_2","first-page":"1601","volume-title":"Fields virology","author":"Collins PL","year":"2007","unstructured":"CollinsPLCroweJE. 2007. 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