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1996-03-09
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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).