title: Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection.
abstract: To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4+ T cells. Polyclonal peripheral blood CD4+ cells were costimulated ex vivo and subjects were given infusions of up to 3 x 1010 activated CD4+ cells. Dose-dependent increases in CD4+ cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4+CCR5+ cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4+Ki-67+ cells increased whereas CD4+ T cells containing T cell-receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T-cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, USA. levinebl@mail.med.upennn.edu
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bernstein
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Aronson
authors.forename: Katia
authors.initials: K
authors.lastname: Schlienger
authors.forename: Julio
authors.initials: J
authors.lastname: Cotte
authors.forename: Steven
authors.initials: S
authors.lastname: Perfetto
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Humphries
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Carolyn
authors.initials: C
authors.lastname: Steffens
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Richard G
authors.initials: RG
authors.lastname: Carroll
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D001781:Blood Component Removal; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous
chemical_list: D019713:Receptors, CCR5