title: Quantitative assessment of the functional plasticity of memory CD8(+) T cells.
abstract: While the functional plasticity of memory CD4(+) T cells has been studied extensively, less is known about this property in memory CD8(+) T cells. Here, we report the direct measurement of plasticity by paired daughter analysis of effector and memory OT-I CD8(+) T cells primed in vivo with ovalbumin. Naïve, effector, and memory OT-I cells were isolated and activated in single-cell culture; then, after the first division, their daughter cells were transferred to new cultures with and without IL-4; expression of IFN-γ and IL-4 mRNAs was measured 5 days later in the resultant subclones. Approximately 40% of clonogenic memory CD8(+) T cells were bipotential in this assay, giving rise to an IL-4(-) subclone in the absence of IL-4 and an IL-4(+) subclone in the presence of IL-4. The frequency of bipotential cells was lower among memory cells than naïve cells but markedly higher than among 8-day effectors. Separation based on high or low expression of CD62L, CD122, CD127, or Ly6C did not identify a phenotypic marker of the bipotential cells. Functional plasticity in memory CD8(+) T-cell populations can therefore reflect modulation at the level of a single memory cell and its progeny.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Baz
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Penny
authors.initials: P
authors.lastname: Groves
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Buttigieg
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Apte
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kienzle
authors.affiliation: Cooperative Research Centre for Vaccine Technology, QIMR Berghofer Medical Research Institute, QLD, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002460:Cell Line; D000066670:Cell Plasticity / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D053699:Interleukin-7 Receptor alpha Subunit; C494192:Ly-6C antigen, mouse; D012333:RNA, Messenger; D019041:L-Selectin; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: CD8+ T cells; IFN-γ ⋅ IL-4; Memory; Plasticity