title: Adoptive transfer of syngeneic T cells in HIV-1 discordant twins indicates rapid regulation of T-cell homeostasis.
abstract: The safety and efficacy of adoptive T-cell transfer (ATT) was tested in the context of viral suppression in syngeneic twins discordant for human immunodeficiency virus type 1 (HIV-1) infection. Human leucocyte antigen-matched T cells of seven HIV-negative twins were obtained by lymphapheresis and immediately transfused into the HIV-infected sibling. Four twins received 12 ATTs each, with a mean of 2.10 +/- 0.97 x 10(9) CD4(+) T cells and 1.74 +/- 0.81 x 10(9) CD8(+) T cells. Additional transfers were performed in three more twin pairs to study the short-term kinetics of transfused syngeneic T cells. Mean CD4(+) T-cell counts increased significantly, by 0.133 +/- 0.136 x 10(9) cells/l at 1 h and 0.144 +/- 0.12 x 10(9) cells/l at 3 h post-transfusion (P < 0.0001). Short-term kinetic studies suggested a rapid clearance of transferred T cells from the peripheral blood within minutes due to a distribution to marginal pools. After a mean follow up of 39 months, however, a sustained increase of the mean CD4(+) T-cell count was observed (from 0.232 x 10(9) to 0.523 x 10(9) cells/l) without changes of plasma viraemia. We conclude that ATT combined with highly active antiretroviral therapy is safe and leads to a considerable increase in CD4(+) T-cell numbers. The clearance kinetics of the transfused cells from peripheral blood indicates a very rapid regulation of T-cell homeostasis in HIV infection.
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Thomas
authors.initials: T
authors.lastname: Dielschneider
authors.forename: Olaf
authors.initials: O
authors.lastname: Degen
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stoehr
authors.forename: Heribert
authors.initials: H
authors.lastname: Knechten
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D003131:Combined Modality Therapy; D004200:Diseases in Twins / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007937:Leukapheresis / Q000379:methods; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008297:Male; D010865:Pilot Projects; D016896:Treatment Outcome; D019562:Viral Load