title: Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4(+) T cells to HIV-infected persons.
abstract: We have previously shown that adoptive transfer of in vitro CD3/CD28 activated autologous CD4(+) T cells results in increased CD4 counts and CD4/CD8 ratios in HIV+ subjects. In this report, analysis of variable beta (Vbeta) chain T cell receptor (TCR) repertoire showed that CD3/CD28 stimulation was able to increase polyclonality within skewed spectra types in vitro. In vivo, two of eight subjects showed increase in TCR diversity and importantly, in no subject did a highly skewed in vivo repertoire emerge. Measurement of proliferative response to alloantigen showed increases following infusions. Response to pharmacological stimulus and lectin via Interferon-gamma ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-gamma response to HIV antigens and peptides declined concurrent with stable or diminishing latent infectious viral load in CD4(+) T cells. These data provide further evidence that adoptive transfer of activated autologous CD4(+) T cells can augment the immune system.
authors.affiliation: Division of Retrovirology, Walter Reed Army Institute of Research, Rockville MD 20850, USA.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bernstein
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Aronson
authors.forename: LaRee
authors.initials: L
authors.lastname: Tracy
authors.forename: Katia
authors.initials: K
authors.lastname: Schlienger
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.forename: Robin
authors.initials: R
authors.lastname: Garner
authors.forename: Julio
authors.initials: J
authors.lastname: Cotte
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zheng
authors.forename: Lena
authors.initials: L
authors.lastname: Winestone
authors.forename: Caroline
authors.initials: C
authors.lastname: Liebig
authors.forename: Lynee M
authors.initials: LM
authors.lastname: Galley
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Richard G
authors.initials: RG
authors.lastname: Carroll
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D007371:Interferon-gamma