title: Superior T memory stem cell persistence supports long-lived T cell memory.
abstract: Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell-like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells.
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, 40, Convent Dr., Bethesda, Maryland 20892, USA. luglie@mail.nih.gov
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Maria H
authors.initials: MH
authors.lastname: Dominguez
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Pratip K
authors.initials: PK
authors.lastname: Chattopadhyay
authors.forename: Diane L
authors.initials: DL
authors.lastname: Bolton
authors.forename: Kaimei
authors.initials: K
authors.lastname: Song
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000276:immunology; D008254:Macaca nemestrina / Q000276:immunology; D039902:Multipotent Stem Cells / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines