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We investigated the potential of influenza A virus (IAV)-specific memory CD8+ T cells from mice to alter their phenotype and function in response to reactivation in the presence of IL-4 and anti\u2013IFN-\u03b3 Ab (type 2 conditions). Compared with naive CD8+ T cells, only a small proportion of IAV-specific memory T cells exhibited phenotypic and functional plasticity after clonal activation under type 2 conditions. The potential for modulation of cell-surface phenotype (CD8\u03b1 expression) was associated with specific epigenetic changes at the Cd8a locus, was greater in central memory T cells than effector memory T cells, and was observed in endogenous memory cells of two TCR specificities. Using a novel technique for intracellular cytokine staining of small clonal populations, we showed that IAV-specific memory CD8+ T cells reactivated under type 2 conditions displayed robust IFN-\u03b3 expression and, unlike naive CD8+ T cells activated under type 2 conditions, produced little IL-4 protein. Secondary activation of memory cells under type 2 conditions increased GATA-3 levels with minimal change in T-bet levels. These data suggest that a small population of memory cells, especially central memory T cells, exhibits plasticity; however, most IAV-specific memory CD8+ T cells resist reprogramming upon reactivation and retain the functional state established during priming.<\/jats:p>","DOI":"10.4049\/jimmunol.1701672","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T13:55:32Z","timestamp":1540562132000},"page":"3282-3293","source":"Crossref","is-referenced-by-count":2,"title":["Limited Phenotypic and Functional Plasticity of Influenza Virus\u2013Specific Memory CD8+ T Cells during Activation in an Alternative Cytokine Environment"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-1423","authenticated-orcid":false,"given":"Kim L","family":"Harland","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0565-7146","authenticated-orcid":false,"given":"Annette","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-3413","authenticated-orcid":false,"given":"Simone","family":"N\u00fcssing","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Hensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-335X","authenticated-orcid":false,"given":"Katherine","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1002-0000","authenticated-orcid":false,"given":"Stephen J","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-3267","authenticated-orcid":false,"given":"Anne","family":"Kelso","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria 3000 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,1]]},"reference":[{"key":"2025030417575201500_r1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0092-8674(02)01139-X","article-title":"Molecular and functional profiling of memory CD8 T cell differentiation","volume":"111","author":"Kaech","year":"2002","journal-title":"Cell"},{"key":"2025030417575201500_r2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1084\/jem.186.6.859","article-title":"Rapid effector function in CD8+ memory T cells","volume":"186","author":"Lalvani","year":"1997","journal-title":"J. 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