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Although a vaccine is available, it is only moderately effective and an improved vaccine is urgently needed. The ability to develop a more effective vaccine has been thwarted by a lack of understanding of the mechanism of vaccine\u2010induced immune protection. Over recent decades, many novel <jats:styled-content style=\"fixed-case\">TB<\/jats:styled-content> vaccines have been developed and almost all have aimed to generate memory <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T cells. In this review, we critically evaluate evidence in the literature that supports the contention that memory <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T cells are the prime mediators of vaccine\u2010induced protection against <jats:styled-content style=\"fixed-case\">TB<\/jats:styled-content>. Because of the lack of robust evidence supporting memory <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T cells in this role, the potential for B\u2010cell antibody and \u201ctrained\u201d innate cells as alternative mediators of protective immunity is explored.<\/jats:p>","DOI":"10.1111\/imcb.12278","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T14:16:51Z","timestamp":1559139411000},"page":"647-655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Beyond memory T cells: mechanisms of protective immunity to tuberculosis infection"],"prefix":"10.1111","volume":"97","author":[{"given":"Pia","family":"Steigler","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative Department of Pathology Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"},{"name":"Wellcome Centre for 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