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We show in this article that although bacille Calmette\u2013Gu\u00e9rin controlled M. tuberculosis growth for 7 wk of infection, the protection was gradually lost as the infection entered the chronic phase. The regrowth of M. tuberculosis coincided with an almost complete disappearance of IL-2\u2013producing CD4 T cells. Booster vaccination with a subunit vaccine (Ag85B-ESAT-6+CAF01) expanded IL-2+ CD4+ T cell coexpressing either TNF-\u03b1 or TNF-\u03b1\/IFN-\u03b3, and the maintenance of this population in the late stage of infection was associated with enhanced control of bacterial growth. The IL-2+ CD4+ T cell subsets were KLRG1\u2212 (nonterminally differentiated), were found to be CD62Lhigh, and further maintained a pronounced proliferative and cytokine-producing potential in the draining lymph nodes, when the animals were challenged 2 y postvaccination. These results suggest that the CD4+ KLRG1\u2212 IL-2\u2013secreting subsets are central memory T cells with the potential to continuously replenish the T cells at the site of infection and prevent attrition and functional exhaustion.<\/jats:p>","DOI":"10.4049\/jimmunol.1300248","type":"journal-article","created":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T04:23:15Z","timestamp":1368678195000},"page":"6311-6319","source":"Crossref","is-referenced-by-count":159,"title":["Control of Chronic <i>Mycobacterium tuberculosis<\/i> Infection by CD4 KLRG1\u2212 IL-2\u2013Secreting Central Memory Cells"],"prefix":"10.1093","volume":"190","author":[{"given":"Thomas","family":"Lindenstr\u00f8m","sequence":"first","affiliation":[{"name":"Tuberculosis Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels Peter Hell","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Tuberculosis Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Else Marie","family":"Agger","sequence":"additional","affiliation":[{"name":"Tuberculosis Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Andersen","sequence":"additional","affiliation":[{"name":"Tuberculosis Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,6,15]]},"reference":[{"key":"2025032407065489500_r1","volume-title":"Global Tuberculosis Control","author":"WHO","year":"2011"},{"key":"2025032407065489500_r2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1542\/peds.96.1.29","article-title":"The efficacy of bacillus Calmette-Gu\u00e9rin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature","volume":"96","author":"Colditz","year":"1995","journal-title":"Pediatrics"},{"key":"2025032407065489500_r3","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/jama.1994.03510330076038","article-title":"Efficacy of BCG vaccine in the prevention of tuberculosis. 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