{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:55:01Z","timestamp":1791215701655,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,4,17]]},"abstract":"<jats:p>\n                    Infection or successful vaccination results in the formation of long-lived memory CD8 T-cell populations. Despite their numerical stability, memory CD8 T-cell populations are thought to completely turn over through proliferation within a 2- to 3-mo period. Therefore, steady-state memory cell proliferation must be balanced by a precisely regulated and equivalent death rate. However, the mechanisms regulating this balancing process remain completely undefined. Herein, we provide evidence for \u201cdeath-intermediate memory cells\u201d (T\n                    <jats:sub>DIM<\/jats:sub>\n                    ) within memory CD8 T-cell populations generated by infection. Importantly, CD62L\n                    <jats:sup>Lo<\/jats:sup>\n                    \/CD27\n                    <jats:sup>Lo<\/jats:sup>\n                    T\n                    <jats:sub>DIM<\/jats:sub>\n                    s are functionally characterized by an inability to produce cytokines, the failure to internalize T-cell receptor following antigenic stimulation, and signatures of apoptotic death. Furthermore, we demonstrate that, mechanistically, T\n                    <jats:sub>DIM<\/jats:sub>\n                    are directly generated from dividing \u201ccentral memory\u201d T-cell populations undergoing memory turnover in vivo. Collectively, these results demonstrate that as central memory CD8 T cells proliferate, they continuously generate a population of CD8 T cells that are nonfunctional and apoptotic; thus, our data support a model wherein division-linked generation of T\n                    <jats:sub>DIM<\/jats:sub>\n                    contributes to numerically stable CD8 T-cell memory.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1118868109","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T01:11:02Z","timestamp":1333415462000},"page":"6199-6204","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Division-linked generation of death-intermediates regulates the numerical stability of memory CD8 T cells"],"prefix":"10.1073","volume":"109","author":[{"given":"Jeffrey C.","family":"Nolz","sequence":"first","affiliation":[{"name":"Departments of aMicrobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Rai","sequence":"additional","affiliation":[{"name":"Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir P.","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Pathology and"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Harty","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and"},{"name":"Pathology and"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 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