Ex vivo expansion of HIV type 1-specific cytolytic T cells from HIV type 1-seropositive subjects.
Cytotoxic T lymphocytes that specifically lyse HIV-1-infected cells occur at uncommonly high frequency in the blood of infected individuals. The CTL response is dominated by the recognition of a small number of peptides encoded by HIV-1 structural and regulatory genes. These two facts have enabled us to develop potent HIV-specific CTL lines from the blood of infected patients without AIDS opportunistic infections by ex vivo culture of nonspecifically stimulated T cell lines with autologous antigen-presenting cells (APCs) preincubated with immunodominant HIV-1 peptides. After one selection, HIV-specific cytotoxicity is enhanced 1.4- to sixfold. Frequency analysis of the T cell line from 1 patient revealed that after exposure to peptide-incubated autologous B-LCLs, the frequency of CTLs specific for the gp160-expressing APCs was enhanced 6-fold and, after a second exposure, 11-fold compared to the nonselected T cell line. Because the APCs used for the frequency analysis were EBV-transformed B-LCLs, some of the specific CTLs in the culture recognized the EBV-expressing APCs. HIV-specific cytotoxicity is enhanced without augmentation of EBV-specific cytotoxicity when PBMCs are used as APCs. Because T cell lines enhanced for HIV-1 specificity are highly cytotoxic and can be expanded to approximately 10(9)-10(10) cells/ml of blood, they may be useful for laboratory research or for immunotherapy.
Lieberman
J
J
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.
Fabry
J A
JA
Shankar
P
P
Beckett
L
L
Skolnik
P R
PR
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015415:Biomarkers; D002460:Cell Line / Q000276:immunology / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D015686:Gene Products, env / Q000096:biosynthesis / Q000737:chemistry; D015488:HIV Antigens / Q000737:chemistry; D019302:HIV Envelope Protein gp160; D006679:HIV Seropositivity / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D016219:Immunotherapy, Adoptive; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000096:biosynthesis / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology* / Q000821:virology
D015415:Biomarkers; D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D016056:Immunodominant Epitopes; D011498:Protein Precursors