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The conventional approach of observing T cells as either T helper or T cytotoxic is overly simplistic and does not allow investigators to clearly identify immune mechanisms or alterations in physiological processes that impact on clinical outcomes. The complexity of T cell sub\u2010populations, as we understand them today, combined with the immunological and functional diversity of these subsets represent significant complications for the study of T cell biology. In this article, we review the use of classical markers in delineating T cell sub\u2010populations, from \u201ctruly na\u00efve\u201d T cells (recent thymic emigrants with no proliferative history) to \u201cexhausted senescent\u201d T cells (poorly proliferative cells that display severe functional abnormalities) wherein the different phenotypes of these populations reflect their disparate functionalities. In addition, since persistent infections and chronological aging have been shown to be associated with significant alterations in human T cell distribution and function, we also discuss age\u2010associated and cytomegalovirus\u2010driven alterations in the expression of key subset markers. \u00a9 2013 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.22351","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T21:47:39Z","timestamp":1381528059000},"page":"25-35","source":"Crossref","is-referenced-by-count":332,"title":["From \u201ctruly na\u00efve\u201d to \u201cexhausted senescent\u201d T cells: When markers predict functionality"],"prefix":"10.1002","volume":"85","author":[{"given":"Anis","family":"Larbi","sequence":"first","affiliation":[{"name":"Singapore Immunology Network (SIgN) Biopolis Agency for Science Technology and Research (A*STAR)  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Fulop","sequence":"additional","affiliation":[{"name":"Department of Medicine Geriatrics Division Research Center on Aging University of Sherbrooke Sherbrooke 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