       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).

