Document 0526
 DOCN  M9590526
 TI    Evidence for the stochastic acquisition of cytokine profile by CD4+ T
       cells activated in a T helper type 2-like response in vivo.
 DT    9509
 AU    Kelso A; Groves P; Troutt AB; Francis K; Walter and Eliza Hall Institute
       of Medical Research, Parkville,; Australia.
 SO    Eur J Immunol. 1995 May;25(5):1168-75. Unique Identifier : AIDSLINE
       MED/95293007
 AB    The diversity of cytokine production patterns displayed by T cells
       activated in vivo was investigated by analyzing short-term
       antigen-specific CD4+ T cell clones and single CD4+ T cells derived from
       draining lymph nodes of mice undergoing a T helper 2 (Th2)-like response
       to keyhole limpet hemocyanin (KLH). On average, 2.7% of CD4+ lymph node
       cells gave rise to clones in the presence of the immunizing antigen and,
       of these, about 90% secreted interleukin-4 (IL-4) and 20% secreted
       interferon-gamma (IFN-gamma) when restimulated after 2 weeks in vitro.
       Almost all IFN-gamma-producing clones co-produced IL-4. The definition
       of clones as positive or negative for cytokine synthesis depended on
       assay sensitivity, however, since their titers were distributed
       continuously from the threshold of detection over at least a 1000-fold
       range. Reverse-transcription polymerase chain reaction analysis of 59
       clones revealed multiple patterns of co-expression of IL-2, IL-3, IL-4,
       IL-6, IFN-gamma and granulocyte-macrophage colony-stimulating factor
       (GM-CSF) mRNA. Although most clones contained detectable IL-4 and IL-6
       mRNA and a minority contained IFN-gamma mRNA, only 1 clone expressed the
       canonical Th2 cytokine profile. The observed frequencies of mRNA
       co-expression for most of the six cytokines (including IL-4 with
       IFN-gamma), and the frequency of co-secretion of IL-4 and IFN-gamma,
       were not significantly different from those predicted for random
       association. Independent regulation of IL-4 and IFN-gamma mRNA
       expression was confirmed at the single-cell level in a polyclonal
       population of KLH-primed CD4+ cells, among which co-expression of these
       cytokines again occurred at the frequency predicted for a random event.
       The data suggest that the polarization of this immune response towards a
       Th2 cytokine profile is achieved by altering the probabilities of
       expression of the IL-4, IFN-gamma and other cytokine genes at the
       population level, rather than by selective expansion of a distinct T
       cell subset.
 DE    Animal  Base Sequence  Female  *Gene Expression Regulation
       Granulocyte-Macrophage Colony-Stimulating Factor/*BIOSYNTHESIS/
       GENETICS  Hemocyanin/*IMMUNOLOGY  Immunization  Interferon Type
       II/*BIOSYNTHESIS/GENETICS  Interleukins/*BIOSYNTHESIS/GENETICS
       *Lymphocyte Transformation  Mice  Mice, Inbred C57BL  Models,
       Immunological  Molecular Sequence Data  Polymerase Chain Reaction  RNA,
       Messenger/BIOSYNTHESIS/GENETICS  Stochastic Processes  Support, Non-U.S.
       Gov't  Th2 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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