Syngeneic adoptive transfer of anti-human immunodeficiency virus (HIV-1)-primed lymphocytes from a vaccinated HIV-seronegative individual to his HIV-1-infected identical twin.
Immunotherapy by adoptive transfer of lymphocytes was attempted in identical twins, one who was virus-free and the other who was infected with human immunodeficiency virus-1 (HIV-1), at the stage of acquired immunodeficiency syndrome. The noninfected twin was vaccinated by priming with a recombinant vaccinia virus expressing the envelope glycoprotein of one of his brother's viruses and boosting with the same purified gp160 adsorbed on alum. Vaccination elicited major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes specific for HIV-1, but no antibody response. The diseased brother, a 38-year-old homosexual who had developed repeated opportunistic infections since 1990 and had a CD4+ count reduced to practically zero, was treated by infusions of lymphocytes collected from the vaccinated brother by lymphopheresis. After a first transfer of the whole lymphocyte population, no changes were observed in the clinical status and biologic or virologic parameters. A second transfer was then applied with activation of the cells with purified envelope glycoprotein before infusion. The outcome of the treatment was an increase in total lymphocytes, in CD4+ and activated CD8+ DR+ cell counts, and in proliferative responses to HIV antigens. A marked but transient 3-log increase in cellular and plasmatic virus loads was also observed after the second adoptive transfer. These observations will be considered with attention to improve the future adoptive transfer protocols, especially in patients with severe CD4+ depletion.
Bex
F
F
Department of Molecular Biology, University of Brussels, Belgium.
Hermans
P
P
Sprecher
S
S
Achour
A
A
Badjou
R
R
Desgranges
C
C
Cogniaux
J
J
Franchioli
P
P
Vanhulle
C
C
Lachgar
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy*; D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D017931:DNA Primers; D004200:Diseases in Twins; D015686:Gene Products, env / Q000096:biosynthesis* / Q000235:genetics; D015752:Genes, env; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014185:Transplantation, Isogeneic; D014430:Twins, Monozygotic; D014611:Vaccination / Q000379:methods
D015703:Antigens, CD; D017931:DNA Primers; D015686:Gene Products, env