Document 0500
 DOCN  M9480500
 TI    Evaluation of human immunodeficiency virus type 1 (HIV-1)-specific
       cytotoxic T-lymphocyte responses utilizing B-lymphoblastoid cell lines
       transduced with the CD4 gene and infected with HIV-1.
 DT    9410
 AU    McElrath MJ; Rabin M; Hoffman M; Klucking S; Garcia JV; Greenberg PD;
       Department of Medicine, University of Washington School of; Medicine,
       Seattle.
 SO    J Virol. 1994 Aug;68(8):5074-83. Unique Identifier : AIDSLINE
       MED/94309173
 AB    Analysis of major histocompatibility complex-restricted cytotoxic T
       lymphocytes (CTL) capable of killing human immunodeficiency virus type 1
       (HIV-1)-infected targets is essential for elucidating the basis for
       HIV-1 disease progression and the potential efficacy of candidate
       vaccines. The use of primary CD4+ T cells with variable infectivity as
       targets for such studies has significant limitations, and immortal
       autologous cells with high levels of CD4 expression that can be
       consistently infected with HIV-1 would be of much greater utility.
       Therefore, we transduced Epstein-Barr-virus-transformed B-lymphoblastoid
       cell lines (LCL) with a retroviral vector, LT4SN, containing the human
       CD4 gene. Stable LCL in which more than 95% of cells expressed membrane
       CD4 were obtained. Aliquots were infected with HIV-1, and, after 4 to 7
       days, nearly all of the cells contained cytoplasmic gag and produced
       high levels of p24 antigen. The ability of major histocompatibility
       complex-restricted CD8+ CTL to lyse such HIV-1-infected CD4-transduced
       LCL (LCL-CD4HIV-1) was evaluated. These autologous targets were lysed by
       CTL generated from an HIV-1-uninfected vaccinee over a broad range of
       effector-to-target ratios. Similarly, the LCL-CD4HIV-1 were efficiently
       lysed by fresh circulating CTL from HIV-1-infected individuals, as well
       as by CTL activated by in vitro stimulation. Both HIV-1 env- and
       gag-specific CTL effectors lysed LCL-CD4HIV-1, consistent with the
       cellular expression of both HIV-1 genes. The LCL-CD4HIV also functioned
       as stimulator cells, and thus are capable of amplifying CTL against
       multiple HIV-1 gene products in HIV-1-infected individuals. The ability
       to produce HIV-1-susceptible autologous immortalized cell lines that can
       be employed as target cells should enable a more detailed evaluation of
       vaccine-induced CTL against both homologous and disparate HIV-1 strains.
       Furthermore, the use of LCL-CD4HIV-1 should facilitate the analysis of
       the range of HIV-1 gene products recognized by CTL in seropositive
       persons.
 DE    Antigens, CD4/GENETICS/*IMMUNOLOGY  AIDS Vaccines/IMMUNOLOGY
       B-Lymphocytes/CYTOLOGY/*IMMUNOLOGY/MICROBIOLOGY  Cell Line, Transformed
       Human  HIV Seropositivity/IMMUNOLOGY  HIV-1/*IMMUNOLOGY/PHYSIOLOGY
       Support, U.S. Gov't, P.H.S.  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY
       Transduction, Genetic  Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).