       Document 0454
 DOCN  M9650454
 TI    Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma
       gondii-infected cells.
 DT    9605
 AU    Montoya JG; Lowe KE; Clayberger C; Moody D; Do D; Remington JS; Talib S;
       Subauste CS; Department of Immunology and Infectious Diseases, Palo
       Alto; Medical Foundation, California 94301, USA.
 SO    Infect Immun. 1996 Jan;64(1):176-81. Unique Identifier : AIDSLINE
       MED/96110931
 AB    Studies to determine if Toxoplasma gondii-specific human T cells lyse
       parasite-infected cells have yielded conflicting results. Furthermore,
       attempts to obtain human cytotoxic CD8+ T lymphocytes have been
       difficult because of the lack of a reproducible system for their
       generation. By using paraformaldehyde-fixed, T. gondii-infected
       peripheral blood mononuclear cells as antigen-presenting cells, we
       developed a method whereby T. gondii-specific T-cell lines can be
       reproducibly generated. Six T. gondii-specific T-cell lines were
       generated from an individual chronically infected with T. gondii.
       Cytofluorometric analysis of these lines revealed > 99% CD3+, 85 to 95%
       CD3+ alpha beta T-cell-receptor-positive (TCR+), 5 to 9% CD3+ gamma
       delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were
       examined during the first 3 weeks of stimulation and >99% CD3+, >99%
       CD3+ alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60
       to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both
       CD4+ and CD8+ T cells had remarkable cytotoxic activity against T.
       gondii-infected target cells (30 to 50% specific Cr release at an
       effector-to-target ratio of 30:1) but not against uninfected target
       cells ( < 10% at an effector-to-target ratio of 30:1). Cytotoxic
       activity by the whole T-cell lines was not T. gondii strain specific.
       Whole T-cell lines were cytotoxic for target cells infected with the C56
       and ME49 strains and the RH strain (which was used to infect peripheral
       blood mononuclear cells). T. gondii-specific T-cell lines displayed the
       predominant expression of V beta 7 TCR. The CDR3 regions of the V beta 7
       TCRs of these T-cell lines showed a striking degree of sequence identity
       (oligoclonality). T-cell lines obtained by the method reporter here can
       be used to characterize functional activity of T-lymphocyte subsets in
       humans infected with T. gondii.
 DE    Amino Acid Sequence  Animal  Base Sequence  Cell Line  Cloning,
       Molecular  Cytotoxicity Tests, Immunologic  Cytotoxicity,
       Immunologic/*GENETICS  CD4-Positive T-Lymphocytes/*IMMUNOLOGY
       CD8-Positive T-Lymphocytes/*IMMUNOLOGY  Flow Cytometry  Gene
       Rearrangement, beta-Chain T-Cell Antigen Receptor  Human  Immunity,
       Natural  Leukocytes, Mononuclear/PARASITOLOGY  Molecular Sequence Data
       Receptors, Antigen, T-Cell, alpha-beta/GENETICS  Sequence Analysis, DNA
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocyte
       Subsets/IMMUNOLOGY  Toxoplasma/*IMMUNOLOGY  JOURNAL ARTICLE

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

