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M9620473.TXT
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1996-02-26
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Document 0473
DOCN M9620473
TI Heterogeneity of intracellular cytokine synthesis at the single-cell
level in polarized T helper 1 and T helper 2 populations.
DT 9602
AU Openshaw P; Murphy EE; Hosken NA; Maino V; Davis K; Murphy K; O'Garra A;
DNAX Research Institute, Palo Alto, California 94304-1104, USA.
SO J Exp Med. 1995 Nov 1;182(5):1357-67. Unique Identifier : AIDSLINE
MED/96042133
AB CD4+ T helper (Th) cells can be classified into different types based on
their cytokine profile. Cells with these polarized patterns of cytokine
production have been termed Th1 and Th2, and can be distinguished
functionally by the production of IFN-gamma and IL-4, respectively.
These phenotypes are crucial in determining the type of immune response
that develops after antigen priming. There are no surface markers that
define them, and cytokine immunoassay or mRNA analysis both have
limitations for characterization of single cells. Using
immunofluorescent detection of intracellular IFN-gamma and IL-4, we have
studied the emergence of Th1 and Th2 cells in response to antigen
exposure and the patterns of cytokine synthesis in established T cell
clones. IFN-gamma production by Th1 clones was detectable in almost all
cells by 4 h, and it continued in most cells for > 24 h. IL-4 production
in Th2 cells peaked at 4 h, but declined rapidly. In Th0 cells
containing both cytokines, fewer cells produced IFN-gamma, which did not
appear until IL-4 synthesis declined. Cocultivation of clones showed no
such cross-regulation. Antigen stimulation of transgenic T cells
expressing an ovalbumin-specific T cell receptor generated Th2 cells,
probably as a result of endogenous IL-4 production. Addition of IL-12
and/or anti-IL-4 caused Th1 cells to develop, while some Th0 cells were
seen when IL-12 alone was added. These results show that stimulation in
the presence of polarizing stimuli results in cells producing either
IFN-gamma or IL-4, but that coproduction can occur in rare cells under
defined conditions.
DE Animal Antigen Presentation Antigens/IMMUNOLOGY Coculture
Comparative Study Gene Expression Regulation Interferon Type
II/*BIOSYNTHESIS/GENETICS Interleukin-12/PHARMACOLOGY
Interleukin-4/*BIOSYNTHESIS/GENETICS Intracellular Fluid/METABOLISM
Ionomycin/PHARMACOLOGY Lymphocyte Transformation Mice Mice, Inbred
BALB C Mice, Transgenic Mitogens/PHARMACOLOGY Ovalbumin/IMMUNOLOGY
Receptors, Antigen, T-Cell, alpha-beta/GENETICS Support, Non-U.S. Gov't
T-Lymphocyte Subsets/DRUG EFFECTS/*METABOLISM Tetradecanoylphorbol
Acetate/PHARMACOLOGY Th1 Cells/DRUG EFFECTS/*METABOLISM Th2 Cells/DRUG
EFFECTS/*METABOLISM JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).