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We comprehensively characterized T cell populations in BCG-vaccinated children over time. Blood from 78 healthy, BCG-vaccinated children representing four age groups (&lt;1\u2009yr, \u22651\u2009yr &lt;2\u2009yr, \u22652\u2009yr &lt;5\u2009yr, \u22655\u2009yr), was stimulated <jats:italic>in vitro<\/jats:italic> for 24\u2009hours and 6 days with live BCG to induce effector and central memory responses. Antigen-specific CD4, CD8, \u03b3\u03b4 and regulatory T cell populations were phenotyped and intracellular and secreted cytokines measured by flow cytometry and multiplex ELISA respectively. Our results demonstrated that populations of na\u00efve T cells predominated in infants, compared to older children. However, BCG-specific effector CD4 T cell responses were equivalent and antigen-specific CD4 T cell proliferative capacity was increased in infants compared to older children. Increases in innate immune responses including \u03b3\u03b4 T cell responses and secreted pro-inflammatory cytokines were noted with increasing age. In conclusion, we identified that the capacity to expand and differentiate effector T cells in response to BCG stimulation wanes with increasing age, which may indicate waning central memory immunity. Booster vaccination could be considered to maintain the antigen-specific central memory pool and possibly enhance the duration of protection.<\/jats:p>","DOI":"10.1038\/s41598-018-33499-4","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T13:53:14Z","timestamp":1539265994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries"],"prefix":"10.1038","volume":"8","author":[{"given":"Elizabeth","family":"Whittaker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Nicol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nontobeko G.","family":"Tena-Coki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Kampmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"33499_CR1","unstructured":"WHO Publication. 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