title: The road to memory: an early rest for the long journey.
abstract: Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA(+), CD127(+), CCR7(+), CD62L(+), CXCR3(+)) first developed into effector T cells (CD45RA(+/-), CD127(+/-), CCR7(+/-), CD62L(+), CXCR3(+)), followed by three intermediate stages: intermediate T cells 1 (CD45RO(+), CD127(+/-), CCR7(+), CD62L(+), CXCR3(+)), intermediate T cells 2 (CD45RO(+), CD127(-), CCR7(-), CD62L(+), CXCR3(+)), and intermediate T cells 3 (CD45RO(+/-), CD127(+), CCR7(+), CD62L(-), CXCR3(+)) before reverting to stable CD45RA(+) central memory T cells (CD45RA(+), CD127(+), CCR7(+), CD62L(+), CXCR3(+)). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO(+), CD127(-), CCR7(-), CD62L(-), CXCR3(+)). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO(+), CCR7(+), CD62L(+)). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore 169608;
authors.forename: Liam Pock
authors.initials: LP
authors.lastname: Ho
authors.forename: Pui San
authors.initials: PS
authors.lastname: Yit
authors.forename: Lee Hui
authors.initials: LH
authors.lastname: Ng
authors.forename: Yeh Ching
authors.initials: YC
authors.lastname: Linn
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Khoon Lin
authors.initials: KL
authors.lastname: Ling
authors.forename: Mickey Boon
authors.initials: MB
authors.lastname: Chai Koh
authors.forename: Meng-Chun
authors.initials: MC
authors.lastname: Monica Shih
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Xue Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Sim Leng
authors.initials: SL
authors.lastname: Tien
authors.forename: Yeow Tee
authors.initials: YT
authors.lastname: Goh
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007239:Infections / Q000276:immunology*; D054400:Receptors, CCR7 / Q000378:metabolism; D054367:Receptors, CXCR3
chemical_list: D015703:Antigens, CD; C515370:CCR7 protein, human; C515187:CXCR3 protein, human; D054400:Receptors, CCR7; D054367:Receptors, CXCR3