{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:27:10Z","timestamp":1773322030434,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,7,22]],"date-time":"2010-07-22T00:00:00Z","timestamp":1279756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Microbiology Vaccine Initiative","award":["R182004067731"],"award-info":[{"award-number":["R182004067731"]}]},{"DOI":"10.13039\/100011512","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>5CD4+CD25+ cells in Mycobacterium chelonae-sensitized mice functionally suppress BCG-induced inflammation, providing one explanation for how immune priming by environmental mycobacteria affects subsequent BCG vaccination responses.<\/jats:p>\n               <jats:p>The efficacy of live Mycobacterium bovis BCG as a tuberculosis vaccine is highly varied globally. Differential sensitization to environmental mycobacteria prior to BCG vaccination may prime immune effects leading to this variation, but the precise immune mechanisms and cell types involved in this phenomenon are unknown. We hypothesized that pre-vaccination sensitization to environmental mycobacteria induces mycobacterium-specific Tregs that suppress responses to BCG. This was investigated by testing Treg responses following priming of BALB\/c mice by i.p. immunization with heat-killed CHE. Such mice produced higher levels of IL-10 before and after intranasal, live BCG administration and had fewer lung inflammatory cells post-BCG, relative to nonsensitized mice. In CHE-sensitized mice, the percentage of splenic CD4+CD25+ cells expressing Foxp3 amongst total lymphocytes was not elevated significantly, but these cells limited nonspecific proliferation of CD4+CD25\u2013 effector cells upon coculture and promoted higher expression levels of CD103 and Foxp3 in response to BCG antigen stimulation than CD4+CD25+ cells from nonsensitized mice. In adoptive transfer experiments, na\u00efve, WT mice receiving CD4+CD25+ cells from CHE-sensitized mice and then given live BCG intranasally had significantly elevated lung IL-10 levels, reduced frequencies of lung IL-2-producing cells, and lower lymphocyte numbers in the BAL. Therefore, CHE sensitization induced CD4+CD25+ Tregs with functional, suppressive activity on BCG responses in vitro and in vivo. Treg induction could therefore be one mechanism underlying how environmental mycobacteria priming modulates host responses to the BCG vaccine.<\/jats:p>","DOI":"10.1189\/jlb.0809582","type":"journal-article","created":{"date-parts":[[2010,7,23]],"date-time":"2010-07-23T03:51:02Z","timestamp":1279857062000},"page":"1073-1080","source":"Crossref","is-referenced-by-count":20,"title":["Regulatory T cells induced by <i>Mycobacterium chelonae<\/i> sensitization influence murine responses to bacille Calmette-Gu\u00e9rin"],"prefix":"10.1093","volume":"88","author":[{"given":"Peiying","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Singapore-MIT Alliance for Research and Technology, Infectious Disease Interdisciplinary Research Group, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geok Teng","family":"Seah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Singapore-MIT Alliance for Research and Technology, Infectious Disease Interdisciplinary Research Group, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,7,22]]},"reference":[{"key":"2023032712152420100_jlb1073-cit-b1","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0140-6736(06)68384-0","article-title":"Global epidemiology of tuberculosis","volume":"367","author":"Dye","year":"2006","journal-title":"Lancet"},{"key":"2023032712152420100_jlb1073-cit-b2","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0140-6736(95)92348-9","article-title":"Variation in protection by BCG: implications of and for heterologous immunity","volume":"346","author":"Fine","year":"1995","journal-title":"Lancet"},{"key":"2023032712152420100_jlb1073-cit-b3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1542\/peds.96.1.29","article-title":"The efficacy of bacillus Calmette-Guerin 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":"2023032712152420100_jlb1073-cit-b4","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1086\/322042","article-title":"Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi","volume":"184","author":"Black","year":"2001","journal-title":"J. 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