Ex vivo expansion of HIV type 1-specific cytolytic T cells from HIV type 1-seropositive subjects

J. Lieberman, J. A. Fabry, P. Shankar, Laurel A Beckett, P. R. Skolnik

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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 109-1010 cells/ml of blood, they may be useful for laboratory research or for immunotherapy.

Original languageEnglish (US)
Pages (from-to)257-271
Number of pages15
JournalAIDS Research and Human Retroviruses
Volume11
Issue number2
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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