Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression.
An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+ T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+ cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.
Koenig
S
S
MedImmune, Inc., Gaithersburg, Maryland 20878, USA.
Conley
A J
AJ
Brewah
Y A
YA
Jones
G M
GM
Leath
S
S
Boots
L J
LJ
Davey
V
V
Pantaleo
G
G
Demarest
J F
JF
Carter
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005784:Gene Amplification; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000032:analysis; D016655:HIV Core Protein p24 / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D004279:DNA, Viral; D015693:Gene Products, nef; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D054311:nef Gene Products, Human Immunodeficiency Virus