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Reactivation of CMV leads to memory inflation, a process in which CD8 T cells expand over time. Memory inflation is associated with specific changes in T cell function, including increased oligoclonality, decreased cytokine production, and terminal differentiation. To address whether memory inflation during the first year after transplantation in human subjects alters T cell differentiation and function, we employed single-cell\u2013matched TCR\u03b1\u03b2 and targeted gene expression sequencing. Expanded T cell clones exhibited a terminally differentiated, immunosenescent, and polyfunctional phenotype whereas rare clones were less differentiated. Clonal expansion occurring between pre- and 3 mo posttransplant was accompanied by enhancement of polyfunctionality. In contrast, polyfunctionality and differentiation state were largely maintained between 3 and 12 mo posttransplant. Highly expanded clones had a higher degree of polyfunctionality than rare clones. Thus, CMV-responsive CD8 T cells differentiated during the pre- to posttransplant period then maintained their differentiation state and functional capacity despite posttransplant clonal expansion.<\/jats:p>","DOI":"10.4049\/jimmunol.2100405","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T13:30:51Z","timestamp":1632317451000},"page":"2086-2095","source":"Crossref","is-referenced-by-count":5,"title":["Functional Consequences of Memory Inflation after Solid Organ Transplantation"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6470-6155","authenticated-orcid":false,"given":"Lauren E","family":"Higdon","sequence":"first","affiliation":[{"name":"Department of Medicine\/Nephrology, Stanford University , Palo Alto, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8842-0218","authenticated-orcid":false,"given":"Steven","family":"Schaffert","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University , Stanford, CA"},{"name":"Department of Medicine\/Biomedical Informatics, Stanford University , Stanford, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2533-3472","authenticated-orcid":false,"given":"Rachel H","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Nephrology, Stanford University , Palo Alto, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-2182","authenticated-orcid":false,"given":"Maria E","family":"Montez-Rath","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Nephrology, Stanford University , Palo Alto, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1669-3385","authenticated-orcid":false,"given":"Marc","family":"Lucia","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University , Stanford, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2526-7150","authenticated-orcid":false,"given":"Naresha","family":"Saligrama","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University , Stanford CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-4465","authenticated-orcid":false,"given":"Kenneth B","family":"Margulies","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-0251","authenticated-orcid":false,"given":"Olivia M","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University , Stanford, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3169-2148","authenticated-orcid":false,"given":"Jane C","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Nephrology, Stanford University , Palo Alto, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-657X","authenticated-orcid":false,"given":"Mark M","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University , Stanford, CA"},{"name":"Howard Hughes Medical Institute, Stanford University School of Medicine , Stanford, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-4708","authenticated-orcid":false,"given":"Purvesh","family":"Khatri","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University , Stanford, CA"},{"name":"Department of Medicine\/Biomedical Informatics, Stanford University , Stanford, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-269X","authenticated-orcid":false,"given":"Jonathan S","family":"Maltzman","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Nephrology, Stanford University , Palo Alto, CA"},{"name":"Veterans Affairs Palo Alto Health Care System , Palo Alto, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2026041420282052500_r1","doi-asserted-by":"crossref","first-page":"d1575","DOI":"10.2741\/jarvis","article-title":"Mechanisms of human cytomegalovirus persistence and latency","volume":"7","author":"Jarvis","year":"2002","journal-title":"Front. 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