{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T02:45:43Z","timestamp":1774406743668,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T00:00:00Z","timestamp":1348617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AI46530"],"award-info":[{"award-number":["AI46530"]}]},{"name":"NIH","award":["AI069121"],"award-info":[{"award-number":["AI069121"]}]},{"name":"American Lung Association DeSouza"},{"name":"FCT (Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia)","award":["PTDC\/SAU-MII\/099102\/2008"],"award-info":[{"award-number":["PTDC\/SAU-MII\/099102\/2008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"Animals lacking the inducible nitric oxide synthase gene (nos2\u2212\/\u2212<\/jats:sup><\/jats:italic>) are less susceptible to Mycobacterium avium<\/jats:italic> strain 25291 and lack nitric oxide\u2010mediated immunomodulation of CD<\/jats:styled-content>4+<\/jats:sup> T<\/jats:styled-content> cells. Here we show that the absence of nos2<\/jats:italic> results in increased accumulation of neutrophils and both CD<\/jats:styled-content>4+<\/jats:sup> and CD<\/jats:styled-content>8+<\/jats:sup> T<\/jats:styled-content> cells within the M<\/jats:styled-content>. avium<\/jats:italic> containing granuloma. Examination of the T<\/jats:styled-content>\u2010cell phenotype in M<\/jats:styled-content>. avium<\/jats:italic> infected mice demonstrated that CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>44hi<\/jats:sup> effector T<\/jats:styled-content> cells expressing the T<\/jats:styled-content>h1 transcriptional regulator T<\/jats:styled-content>\u2010bet (T<\/jats:styled-content>\u2010bet+<\/jats:sup>) were specifically reduced by the presence of nitric oxide. Importantly, the T<\/jats:styled-content>\u2010bet+<\/jats:sup> effector population could be separated into CD<\/jats:styled-content>69hi<\/jats:sup> and CD<\/jats:styled-content>69lo<\/jats:sup> populations, with the CD<\/jats:styled-content>69lo<\/jats:sup> population only able to accumulate during chronic infection within infected nos2\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. Transcriptomic comparison between CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>44hi<\/jats:sup>CD<\/jats:styled-content>69hi<\/jats:sup> and CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>44hi<\/jats:sup>CD<\/jats:styled-content>69lo<\/jats:sup> populations revealed that CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>44hi<\/jats:sup>CD<\/jats:styled-content>69lo<\/jats:sup> cells had higher expression of the integrin itgb1\/itga4<\/jats:italic> (VLA<\/jats:styled-content>\u20104, CD<\/jats:styled-content>49d\/CD<\/jats:styled-content>29). Inhibition of N<\/jats:styled-content>os2 activity allowed increased accumulation of the CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>44hi<\/jats:sup>T<\/jats:styled-content>\u2010bet+<\/jats:sup>CD<\/jats:styled-content>69lo<\/jats:sup> population in WT<\/jats:styled-content> mice as well as increased expression of VLA<\/jats:styled-content>\u20104. These data support the hypothesis that effector T<\/jats:styled-content> cells in mycobacterial granulomata are not a uniform effector population but exist in distinct subsets with differential susceptibility to the regulatory effects of nitric oxide.<\/jats:p>","DOI":"10.1002\/eji.201142158","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T07:07:18Z","timestamp":1344928038000},"page":"3267-3279","source":"Crossref","is-referenced-by-count":27,"title":["Nitric oxide inhibits the accumulation of CD<\/scp>4+<\/sup>CD<\/scp>44hi<\/sup>T<\/scp>bet+<\/sup>CD<\/scp>69lo<\/sup>T<\/scp> cells in mycobacterial infection"],"prefix":"10.1002","volume":"42","author":[{"given":"John E.","family":"Pearl","sequence":"first","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"}]},{"given":"Egidio","family":"Torrado","sequence":"additional","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"}]},{"given":"Michael","family":"Tighe","sequence":"additional","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"}]},{"given":"Jeffrey J.","family":"Fountain","sequence":"additional","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"}]},{"given":"Alejandra","family":"Solache","sequence":"additional","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"},{"name":"Millipore Temecula CA USA"}]},{"given":"Tara","family":"Strutt","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Medical School Worcester MA USA"}]},{"given":"Susan","family":"Swain","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Medical School Worcester MA USA"}]},{"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular (IBMC) University of Porto Portugal"}]},{"given":"Andrea M.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Trudeau Institute Inc. Saranac Lake NY USA"}]}],"member":"311","published-online":{"date-parts":[[2012,9,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132703"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119782"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)02344-2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.058446"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.4049\/jimmunol.162.11.6734","article-title":"Improved clearance of \n Mycobacterium avium upon disruption of the inducible nitric oxide synthase gene","volume":"162","author":"Gomes M. S.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_8_8_1","first-page":"1","volume-title":"Methods in Molecular Biology","author":"Hirst D.","year":"2011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290267"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2741\/2322"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(00)00238-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.1.L116"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2222"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-869-0_24"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009781200"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1128\/IAI.67.7.3334-3338.1999","article-title":"T\u2010cell responses during \n Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase","volume":"67","author":"Millar A. 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