title: HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo.
abstract: Most HIV+ individuals require lifelong highly active antiretroviral therapy (HAART) to suppress HIV replication, but fail to eliminate the virus in part because of residual replication in gut-associated lymphoid tissues (GALT). Naturally elicited HIV-specific CD8+ T cells generated in the acute and chronic infectious phases exhibit antiviral activity, but decrease in number after HAART. Therapeutic vaccines represent a potential strategy to expand cellular responses, although previous efforts have been largely unsuccessful, conceivably because of a lack of responding HIV-specific central-memory CD8+ T cells (Tcm). To determine whether patients receiving HAART possess CD8+ T cells with Tcm qualities that are amenable to augmentation, HIV-specific CD8+ T-cell clones were derived from HIV-reactive CD28+CD8+ T-cell lines isolated from 7 HIV+ HAART-treated patients, expanded ex vivo, and reinfused into their autologous host. Tracking of the cells in vivo revealed that clones could persist for ≥ 84 days, maintain expression and/or re-express CD28, up-regulate CD62L, secrete IL-2, proliferate on cognate Ag encounter and localize to the rectal mucosa. These results suggest some infused cells exhibited phenotypic and functional characteristics shared with Tcm in vivo, and imply that more effective therapeutic vaccination strategies targeting CD8+ Tcm in patients on HAART might provide hosts with expanded, long-lasting immune responses not only systemically but also in GALT.
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA.
authors.forename: Aude G
authors.initials: AG
authors.lastname: Chapuis
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.forename: Steve
authors.initials: S
authors.lastname: Kuntz
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: Annelie
authors.initials: A
authors.lastname: Tjernlund
authors.forename: Kurt
authors.initials: K
authors.lastname: Diem
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Turtle
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Cigal
authors.forename: Roxanne
authors.initials: R
authors.lastname: Velez
authors.forename: Stanley
authors.initials: S
authors.lastname: Riddell
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000628:therapy; D006801:Humans; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D012007:Rectum / Q000276:immunology / Q000473:pathology; D014182:Transplantation, Autologous
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D018106:CD28 Antigens; D000939:Epitopes; D015488:HIV Antigens; C508594:IL2 protein, human; D007376:Interleukin-2