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Versus IL-4 and IL-10: Selective Induction of IL-10 by Sequential Stimulation of Naive Th Cells with IL-12 and IL-41
*
Institute for Genetics, University of Cologne, Zentrum für Molekularbiologische Medizin, Cologne, Germany, and Deutsches Rheuma-Forschungszentrum, Berlin, Germany; and
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
Commitment of Th lymphocytes to the Th1 phenotype, as characterized
by the expression of the major proinflammatory cytokine IFN-
, may be
critically involved in the establishment of chronic inflammation and
inflammatory autoimmune disease. To date, it has been shown that in
IL-12-stimulated murine Th cell lines containing a major fraction of
Th1 cells, Th2 cells can be induced by IL-4 until about 2 wk after
initial activation, but not later. Here we analyze, based on the
magnetic isolation of viable Th1 cells according to their specific
expression of IFN-, the cytokine commitment of individual Th1 cells.
After activation of naive Th cells with Ag and IL-12 for up to 5 wk,
isolated IFN--producing cells were restimulated with Ag and IL-4.
Within the first 3 to 4 wk of IL-12 stimulation, some
IFN-+ cells stopped expression of IFN- when
restimulated with IL-4. However, within only 1 to 2 wk of IL-12
stimulation, few IFN-+ cells could be converted to
produce IL-4. Others continued to express IFN- and thus were already
committed to a proinflammatory, Th1-like phenotype. Surprisingly,
within 3 wk of IL-12 stimulation, many of the IFN--producing cells
responded to IL-4 restimulation by expression of IL-10, but neither
IFN- nor IL-4, i.e., by conversion to a suppressive,
anti-inflammatory phenotype.
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